{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:33:06Z","timestamp":1792153986104,"version":"4.4.0"},"reference-count":251,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer death worldwide. Early detection of lung cancer can lead to identification of the cancer at its initial treatable stages and improves survival. Low-dose CT scan (LDCT) is currently the gold standard for lung cancer screening in high-risk individuals. Despite the observed stage migration and consistently demonstrated disease-specific overall survival benefit, LDCT has inherent limitations, including false-positive results, radiation exposure, and low compliance. Recently, new techniques have been investigated for early detection of lung cancer. Several studies have shown that liquid biopsy biomarkers such as circulating cell-free DNA (cfDNA), microRNA molecules (miRNA), circulating tumor cells (CTCs), tumor-derived exosomes (TDEs), and tumor-educated platelets (TEPs), as well as volatile organic compounds (VOCs), have the power to distinguish lung cancer patients from healthy subjects, offering potential for minimally invasive and non-invasive means of early cancer detection. Furthermore, recent studies have shown that the integration of artificial intelligence (AI) with clinical, imaging, and laboratory data has provided significant advancements and can offer potential solutions to some challenges related to early detection of lung cancer. Adopting AI-based multimodality strategies, such as multi-omics liquid biopsy and\/or VOCs\u2019 detection, with LDCT augmented by advanced AI, could revolutionize early lung cancer screening by improving accuracy, efficiency, and personalization, especially when combined with patient clinical data. However, challenges remain in validating, standardizing, and integrating these approaches into clinical practice. In this review, we described these innovative milestones and methods, as well as their advantages and limitations in screening and early diagnosis of lung cancer.<\/jats:p>","DOI":"10.3390\/jcm14217812","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T19:30:27Z","timestamp":1762198227000},"page":"7812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Early Detection of Lung Cancer: A Review of Innovative Milestones and Techniques"],"prefix":"10.3390","volume":"14","author":[{"given":"Faisal M.","family":"Habbab","sequence":"first","affiliation":[{"name":"Division of Radiation Oncology, Department of Oncology, University of Alberta, Edmonton, AB T6G 2B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric L. R.","family":"B\u00e9dard","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery, University of Alberta, Edmonton, AB T6G 2B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4201-8930","authenticated-orcid":false,"given":"Anil A.","family":"Joy","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Oncology, University of Alberta, Edmonton, AB T6G 2B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarmina","family":"Alam","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, Department of Oncology, University of Alberta, Edmonton, AB T6G 2B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aswin G.","family":"Abraham","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, Department of Oncology, University of Alberta, Edmonton, AB T6G 2B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson H. Y.","family":"Roa","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, Department of Oncology, University of Alberta, Edmonton, AB T6G 2B7, Canada"},{"name":"Division of Medical Oncology, Department of Oncology, University of Alberta, Edmonton, AB T6G 2B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","unstructured":"American Cancer Society (2025, July 28). Key Statistics for Lung Cancer\/How Common Is Lung Cancer?. Available online: https:\/\/www.cancer.org\/cancer\/types\/lung-cancer\/about\/key-statistics.html."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.jtho.2024.02.011","article-title":"The International Association for the Study of Lung Cancer lung cancer staging project: Proposals for revision of the TNM stage groups in the forthcoming (ninth) edition of the TNM classification for lung cancer","volume":"19","author":"Nishimura","year":"2024","journal-title":"J. Thorac. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1378\/chest.86.1.44","article-title":"Screening for early lung cancer. Results of the Memorial Sloan-Kettering study in New York","volume":"86","author":"Melamed","year":"1984","journal-title":"Chest"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1097\/00043764-198608000-00038","article-title":"Lung cancer screening: The Mayo program","volume":"28","author":"Fontana","year":"1986","journal-title":"J. Occup. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1038\/sj.bjc.6605660","article-title":"Lung cancers screening","volume":"102","author":"Pastorino","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"The National Lung Screening Trial Research Team (2011). Reduced lung cancer mortality with low-dose computed tomographic screening. N. Engl. J. Med., 365, 395\u2013409.","DOI":"10.1056\/NEJMoa1102873"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1056\/NEJMoa1911793","article-title":"Reduced lung cancer mortality with volume CT screening in a randomized trial","volume":"382","author":"Scholten","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bonney, A., Malouf, R., Marchal, C., Manners, D., Fong, K.M., Marshall, H.M., Irving, L.B., and Manser, R. (2022). Impact of low-dose computed tomography (LDCT) screening on lung cancer related mortality. Cochrane Database Syst. Rev., 8.","DOI":"10.1002\/14651858.CD013829.pub2"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1200\/JCO.23.01780","article-title":"Pack-year smoking history: An inadequate and biased measure to determine lung cancer screening eligibility","volume":"42","author":"Potter","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1148\/radiol.2019190905","article-title":"Cancer risk in subsolid nodules in the National Lung Screening Trial","volume":"293","author":"Hammer","year":"2019","journal-title":"Radiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1001\/jama.2021.0377","article-title":"Screening for lung cancer with low-dose computed tomography: Updated evidence report and systematic review for the us preventive services task force","volume":"325","author":"Jonas","year":"2021","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"445","DOI":"10.7326\/M14-1352","article-title":"Balancing the benefits and harms of low-dose computed tomography screening for lung cancer: Medicare\u2019s options for coverage","volume":"161","author":"Wiener","year":"2014","journal-title":"Ann. Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rampinelli, C., De Marco, P., Origgi, D., Nicoletti, R., Solli, I., Zappa, M., Tiseo, M., Malvezzi, I., De Pas, M., and Picozzi, G. (2017). Exposure to low dose computed tomography for lung cancer screening and risk of cancer: Secondary analysis of trial data and risk-benefit analysis. BMJ, 356.","DOI":"10.1136\/bmj.j347"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Huang, L., Rong, Y., Tang, X., Yi, K., Wu, J., and Wang, F. (2021). Circular RNAs are promising biomarkers in liquid biopsy for the diagnosis of non-small cell lung cancer. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.625722"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.lungcan.2019.06.016","article-title":"Circulating tumor cell clusters are a potential biomarker for detection of non-small cell lung cancer","volume":"134","author":"Manjunath","year":"2019","journal-title":"Lung Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lee, K.B., Ang, L., Yau, W.P., and Seow, W.J. (2020). Association between metabolites and the risk of lung cancer: A systematic literature review and meta-analysis of observational studies. Metabolites, 10.","DOI":"10.3390\/metabo10090362"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.lungcan.2022.12.002","article-title":"Diagnostic test accuracy of artificial intelligence-based imaging for lung cancer screening: A systematic review and meta-analysis","volume":"176","author":"Thong","year":"2023","journal-title":"Lung Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Smith-Bindman, R., Chu, P.W., Firdaus, H.A., Stewart, C., Malekhedayat, M., Alber, S., Bolch, W.E., Mahendra, M., de Gonz\u00e1lez, A.B., and Miglioretti, D.L. (2025). Projected Lifetime Cancer Risks from Current Computed Tomography Imaging. JAMA Intern. Med., 14.","DOI":"10.1001\/jamainternmed.2025.0505"},{"key":"ref_20","unstructured":"Radiological Society of North America (RSNA)\/American College of Radiology (ACR) (2025, September 24). Radiation Dose in X-Ray and CT Exams. Radiology Info.org. Available online: https:\/\/www.brookeimaging.ca\/sfty_xray.pdf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"242","DOI":"10.7326\/0003-4819-157-4-201208210-00004","article-title":"Predictive accuracy of the Liverpool Lung Project risk model for stratifying patients for computed tomography screening for lung cancer: A case-control and cohort validation study","volume":"157","author":"Raji","year":"2012","journal-title":"Ann. Intern. Med."},{"key":"ref_22","unstructured":"Wood, D.E., Kazerooni, E.A., Aberle, D.R., Baines, J., Boer, B., Brown, L.M., D\u2019Amico, T.A., Detterbeck, F.C., Ettinger, D.S., and Ezer, N. (2025, July 28). Lung Cancer Screening, Version 1.2025, NCCN Clinical Practice Guidelines in Oncology. Available online: https:\/\/www.nccn.org\/guidelines\/category_2."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jtho.2020.10.127","article-title":"Lung Screening Benefits and Challenges: A Review of The Data and Outline for Implementation","volume":"16","author":"Sands","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1056\/NEJMoa1211776","article-title":"Selection criteria for lung-cancer screening","volume":"368","author":"Katki","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e427","DOI":"10.1016\/j.chest.2021.06.063","article-title":"Screening for lung cancer: CHEST guideline and expert panel report","volume":"160","author":"Mazzone","year":"2021","journal-title":"Chest"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ten Haaf, K., van der Aalst, C.M., de Koning, H.J., Kaaks, R., and Tammem\u00e4gi, M.C. (2017). Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study. PLoS Med., 14.","DOI":"10.1371\/journal.pmed.1002277"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"330","DOI":"10.7326\/M13-2771","article-title":"Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement","volume":"160","author":"Moyer","year":"2014","journal-title":"Ann. Intern. Med."},{"key":"ref_28","first-page":"184","article-title":"Cancer screening in the United States, 2019: A review of current American Cancer Society guidelines and current issues in cancer screening","volume":"69","author":"Smith","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"412","DOI":"10.6004\/jnccn.2018.0020","article-title":"Lung cancer screening, version 3.2018, NCCN clinical practice guidelines in oncology","volume":"16","author":"Wood","year":"2018","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1164\/rccm.201408-1475OC","article-title":"Long-term follow-up results of the DANTE trial, a randomized study of lung cancer screening with spiral computed tomography","volume":"191","author":"Infante","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1164\/rccm.201505-1040OC","article-title":"Results of the randomized Danish Lung Cancer Screening trial with focus on high-risk profiling","volume":"193","author":"Wille","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta20400","article-title":"The UK lung cancer screening trial: A pilot randomized controlled trial of low-dose computed tomography screening for the early detection of lung cancer","volume":"20","author":"Field","year":"2016","journal-title":"Health Technol. Assess."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1136\/thoraxjnl-2016-209825","article-title":"Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial","volume":"72","author":"Paci","year":"2017","journal-title":"Thorax"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1093\/annonc\/mdz117","article-title":"Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: New confirmation of lung cancer screening efficacy","volume":"30","author":"Pastorino","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1002\/ijc.32486","article-title":"Lung cancer mortality reduction by LDCT screening\u2014Results from the randomized German LUSI trial","volume":"146","author":"Becker","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/sj.bjc.6604158","article-title":"The LLP risk model: An individual risk prediction model for lung cancer","volume":"98","author":"Cassidy","year":"2008","journal-title":"Br. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ejca.2020.04.035","article-title":"Systematic review and meta-analysis on the impact of lung cancer screening by low-dose computed tomography","volume":"134","author":"Sadate","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1001\/jama.2021.1117","article-title":"US Preventive Services Task Force. Screening for lung cancer: US Preventive Services Task Force recommendation statement","volume":"325","author":"Krist","year":"2021","journal-title":"JAMA"},{"key":"ref_39","first-page":"50","article-title":"Cancer Screening for lung cancer: 2023 guideline update from the American Cancer Society","volume":"74","author":"Wolf","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1097\/CPM.0b013e31827a30c1","article-title":"Risks of transthoracic needle biopsy: How high?","volume":"20","author":"Wiener","year":"2013","journal-title":"Clin. Pulm. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gierada, D.S., Pinsky, P., Nath, H., Chiles, C., Duan, F., and Aberle, D.R. (2014). Projected outcomes using different nodule sizes to define a positive CT lung cancer screening examination. J. Natl. Cancer Inst., 106.","DOI":"10.1093\/jnci\/dju284"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1097\/RLI.0b013e318250a5aa","article-title":"Computer-aided nodule detection and volumetry to reduce variability between radiologists in the interpretation of lung nodules at low-dose screening computed tomography","volume":"47","author":"Jeon","year":"2012","journal-title":"Investig. Radiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1136\/thoraxjnl-2017-210770","article-title":"Disagreement of diameter and volume measurements for pulmonary nodule size estimation in CT lung cancer screening","volume":"73","author":"Heuvelmans","year":"2018","journal-title":"Thorax"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"52","DOI":"10.21037\/tlcr.2017.01.05","article-title":"Volume versus diameter assessment of small pulmonary nodules in CT lung cancer screening","volume":"6","author":"Han","year":"2017","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1148\/radiol.2312030167","article-title":"Are two-dimensional CT measurements of small noncalcified pulmonary nodules reliable?","volume":"231","author":"Revel","year":"2004","journal-title":"Radiology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.2214\/AJR.20.24807","article-title":"Lung-RADS version 1.1: Challenges and a look ahead, from the AJR special series on radiology reporting and data systems","volume":"216","author":"Chelala","year":"2021","journal-title":"Am. J. Roentgenol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Snoeckx, A., Silva, M., Prosch, H., Biederer, J., Frauenfelder, T., Gleeson, F., Jacobs, C., Kauczor, H.U., Parkar, A.P., and Schaefer-Prokop, C. (2025). Lung cancer screening with low-dose CT: Definition of positive, indeterminate, and negative screen results. A nodule management recommendation from the European Society of Thoracic Imaging. Eur. Radiol., ahead of print.","DOI":"10.1007\/s00330-025-11648-4"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.jacr.2023.09.009","article-title":"ACR Lung-RADS v2022: Assessment Categories and Management Recommendations","volume":"21","author":"Christensen","year":"2024","journal-title":"J. Am. Coll. Radiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1002\/cncr.28833","article-title":"Impact of lung cancer screening results on participant health-related quality of life and state anxiety in the National Lung Screening Trial","volume":"120","author":"Gareen","year":"2014","journal-title":"Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1183\/09031936.00123410","article-title":"Long-term effects of lung cancer computed tomography screening on health-related quality of life: The NELSON trial","volume":"38","author":"Borsboom","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.lungcan.2021.12.020","article-title":"Procedural complications associated with invasive diagnostic procedures after lung cancer screening with low-dose computed tomography","volume":"165","author":"Yang","year":"2022","journal-title":"Lung Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jacr.2021.09.015","article-title":"Total and out-of-pocket costs of procedures after lung cancer screening in a national commercially insured population: Estimating an episode of care","volume":"19","author":"Tailor","year":"2022","journal-title":"J. Am. Coll. Radiol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"McAllister, B.J., Malhotra Mukhtyar, R., Cai, S., Brown, K., Lock, S., and Khan, S. (2025). Relationship between household air pollution and lung cancer in never smokers in high-income countries: A systematic review. BMC J. Open, 15.","DOI":"10.1136\/bmjopen-2024-093870"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ji, G., Bao, T., Li, Z., Tang, H., Liu, D., Yang, P., Li, W., and Huang, Y. (2021). Current lung cancer screening guidelines may miss high-risk population: A real-world study. BMC Cancer, 21.","DOI":"10.1186\/s12885-020-07750-z"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41571-020-0393-z","article-title":"Liquid biopsy for early-stage lung cancer moves ever closer","volume":"17","author":"Rolfo","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.21037\/tlcr-20-808","article-title":"Latest CT technologies in lung cancer screening: Protocols and radiation dose reduction","volume":"10","author":"Vonder","year":"2021","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1148\/radiol.210551","article-title":"Deep learning reconstruction shows better lung nodule detection for ultra-low-dose chest CT","volume":"303","author":"Jiang","year":"2022","journal-title":"Radiology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1002\/mp.14142","article-title":"Comparison of conventional chest x ray with a novel projection technique for ultra-low dose CT","volume":"48","author":"Carey","year":"2021","journal-title":"Med. Phys."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Pan, Z., Zhang, Y., Zhang, L., Wang, L., Zhao, K., Li, Q., Wang, A., Hu, Y., and Xie, X. (2024). Detection, measurement, and diagnosis of lung nodules by ultra-low-dose CT in lung cancer screening: A systematic review. BJR Open, 22.","DOI":"10.1093\/bjro\/tzae041"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13244-024-01888-1","article-title":"Ultra-low dose dual-layer detector spectral CT for pulmonary nodule screening: Image quality and diagnostic performance","volume":"16","author":"Ding","year":"2025","journal-title":"Insights Imaging"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12943-022-01505-z","article-title":"Liquid biopsy in lung cancer: Significance in diagnostics, prediction, and treatment monitoring","volume":"21","author":"Li","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Chang, L., Li, J., and Zhang, R. (2022). Liquid biopsy for early diagnosis of non-small cell lung carcinoma: Recent research and detection technologies. Biochim. Biophys. Acta Rev. Cancer, 1877.","DOI":"10.1016\/j.bbcan.2022.188729"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41586-020-2140-0","article-title":"Integrating genomic features for non-invasive early lung cancer detection","volume":"580","author":"Chabon","year":"2020","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.ccell.2017.01.002","article-title":"Liquid Biopsies, What We Do Not Know (Yet)","volume":"31","author":"Bardelli","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4737","DOI":"10.7150\/thno.42565","article-title":"Size profile of cell-free DNA: A beacon guiding the practice and innovation of clinical testing","volume":"10","author":"Shi","year":"2020","journal-title":"Theranostics"},{"key":"ref_66","first-page":"646","article-title":"Free DNA in the serum of cancer patients and the effect of therapy","volume":"37","author":"Leon","year":"1977","journal-title":"Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Li, Y.Z., Kong, S.N., Liu, Y.P., Yang, Y., and Zhang, H.M. (2023). Can liquid biopsy based on ctDNA\/cfDNA replace tissue biopsy for the precision treatment of EGFR-mutated NSCLC?. J. Clin. Med., 12.","DOI":"10.3390\/jcm12041438"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"107458","DOI":"10.1016\/j.pharmthera.2019.107458","article-title":"Circulating tumor DNA as an early cancer detection tool","volume":"207","author":"Weitzel","year":"2020","journal-title":"Pharm. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Underhill, H.R., Kitzman, J.O., Hellwig, S., Welker, N.C., Daza, R., Baker, D.N., Gligorich, K.M., Rostomily, R.C., Bronner, M.P., and Shendure, J. (2016). Fragment length of circulating tumor DNA. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006162"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Bittla, P., Kaur, S., Sojitra, V., Zahra, A., Hutchinson, J., Folawemi, O., and Khan, S. (2023). Exploring circulating tumor DNA (CtDNA) and its role in early detection of cancer: A systematic review. Cureus, 15.","DOI":"10.7759\/cureus.45784"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1373\/clinchem.2004.039263","article-title":"Quantitative Analysis of Circulating Plasma DNA as a Tumor Marker in Thoracic Malignancies","volume":"51","author":"Herrera","year":"2005","journal-title":"Clin. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.lungcan.2009.06.021","article-title":"Circulating DNA is a non-invasive prognostic factor for survival in non-small cell lung cancer","volume":"68","author":"Hol","year":"2010","journal-title":"Lung Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/bjc.2015.225","article-title":"Cell-free DNA levels in plasma of patients with non-small-cell lung cancer and inflammatory lung disease","volume":"113","author":"Szpechcinski","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.canlet.2016.02.002","article-title":"Plasma cell-free DNA levels and integrity in patients with chest radiological findings: NSCLC versus benign lung nodules","volume":"374","author":"Szpechcinski","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.jmoldx.2018.06.008","article-title":"ElectricField\u2013Induced Release and Measurement Liquid Biopsy for Noninvasive Early Lung Cancer Assessment","volume":"20","author":"Wei","year":"2018","journal-title":"J. Mol. Diagn."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1093\/annonc\/mdy458","article-title":"Nanoscale extracellular vesicle-derived DNA is superior to circulating cell-free DNA for mutation detection in early-stage non-small-cell lung cancer","volume":"29","author":"Wan","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Tailor, T.D., Rao, X., Campa, M.J., Wang, J., Gregory, S.G., and Patz, E.F. (2019). Whole Exome Sequencing of Cell-Free DNA for Early Lung Cancer: A Pilot Study to Differentiate Benign From Malignant CT-Detected Pulmonary Lesions. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00317"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Locke, W.J., Guanzon, D., Ma, C., Liew, Y.J., Duesing, K.R., Fung, K.Y., and Ross, J.P. (2019). DNA methylation cancer biomarkers: Translation to the clinic. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.01150"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s10571-016-0447-z","article-title":"The role of DNA methylation in lens development and cataract formation","volume":"37","author":"Wang","year":"2017","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Zhao, J., Lu, Y., Ren, X., Bian, T., Feng, J., Sun, H., Liu, L., She, B., Liu, Y., and Ke, H. (2024). Association of the SHOX2 and RASSF1A methylation levels with the pathological evolution of early-stage lung adenocarcinoma. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12452-x"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1158\/0008-5472.CAN-05-3408","article-title":"Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort","volume":"66","author":"Belinsky","year":"2006","journal-title":"Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13148-022-01337-0","article-title":"Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer","volume":"14","author":"Li","year":"2022","journal-title":"Clin. Epigenet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1186\/s12967-024-05420-3","article-title":"Hypermethylated TAGMe as a universal-cancer-only methylation marker and its application in diagnosis and recurrence monitoring of urothelial carcinoma","volume":"22","author":"Yang","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_84","first-page":"1371","article-title":"Early Detection of Lung Cancer using DNA Promoter Hypermethylation in Plasma and Sputum","volume":"23","author":"Hulbert","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1158\/2159-8290.CD-21-1252","article-title":"The Origin of Highly Elevated Cell-Free DNA in Healthy Individuals and Patients with Pancreatic, Colorectal, Lung, or Ovarian Cancer","volume":"13","author":"Mattox","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0009-8981(02)00337-6","article-title":"Elevated cell free serum DNA detected in patients with myocardial infarction","volume":"327","author":"Chang","year":"2003","journal-title":"Clin. Chim. Acta"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1196\/annals.1368.035","article-title":"Circulating Nucleic Acids and Critical Illness","volume":"1075","author":"Rainer","year":"2006","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Fiala, C., and Diamandis, E.P. (2018). Utility of circulating tumor DNA in cancer diagnostics with emphasis on early detection. BMC Med., 16.","DOI":"10.1186\/s12916-018-1157-9"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41571-018-0058-3","article-title":"Early-stage NSCLC\u2014Challenges to implementing ctDNA-based screening and MRD detection","volume":"15","author":"Abbosh","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nature22364","article-title":"Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution","volume":"545","author":"Abbosh","year":"2017","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/nrclinonc.2017.14","article-title":"Integrating liquid biopsies into the management of cancer","volume":"14","author":"Siravegna","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, Biogenesis, Mechanism, and Function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Shi, Y., Liu, Z., Lin, Q., Luo, Q., Cen, Y., Li, J., Fang, X., and Gong, C. (2021). MiRNAs and Cancer: Key Link in Diagnosis and Therapy. Genes, 12.","DOI":"10.3390\/genes12081289"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrc1840","article-title":"Oncomirs\u2014microRNAs with a role in cancer","volume":"6","author":"Slack","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nrclinonc.2014.5","article-title":"Clinical relevance of circulating cell-free microRNAs in cancer","volume":"11","author":"Schwarzenbach","year":"2014","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"E15","DOI":"10.25011\/cim.v44i1.36016","article-title":"A Novel Composite Biomarker Panel for Detection of Early-Stage Non-small Cell Lung Cancer","volume":"44","author":"Bedard","year":"2021","journal-title":"Clin. Investig. Med."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Freitas, C., Sousa, C., Machado, F., Serino, M., Santos, V., Cruz-Martins, N., Teixeira, A., Cunha, A., Pereira, T., and Oliveira, H.P. (2021). The Role of Liquid Biopsy in Early Diagnosis of Lung Cancer. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.634316"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Roa, W.H., Kim, J.O., Razzak, R., Du, H., Guo, L., Singh, R., Gazala, S., Ghosh, S., Wong, E., and Joy, A.A. (2012). Sputum microRNA profiling: A novel approach for the early detection of non-small cell lung cancer. Clin. Investig. Med., 35.","DOI":"10.25011\/cim.v35i5.18700"},{"key":"ref_99","first-page":"1873","article-title":"Non-small cell lung cancer detection using microRNA expression profiling of bronchoalveolar lavage fluid and sputum","volume":"35","author":"Kim","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.3747\/co.23.2830","article-title":"MicroRNA expression profiling of sputum for the detection of early and locally advanced non-small-cell lung cancer: A prospective case-control study","volume":"23","author":"Razzak","year":"2016","journal-title":"Curr. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Vykoukal, J., Fahrmann, J.F., Patel, N., Shimizu, M., Ostrin, E.J., Dennison, J.B., Ivan, C., Goodman, G.E., Thornquist, M.D., and Barnett, M.J. (2022). Contributions of Circulating MicroRNAs for Early Detection of Lung Cancer. Cancers, 14.","DOI":"10.3390\/cancers14174221"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.soncn.2017.03.001","article-title":"Screening and Early Detection of Lung Cancer","volume":"33","author":"Eggert","year":"2017","journal-title":"Semin. Oncol. Nurs."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.cllc.2014.12.006","article-title":"Early Detection of Lung Cancer in Serum by a Panel of MicroRNA Biomarkers","volume":"16","author":"Wang","year":"2015","journal-title":"Clin. Lung Cancer"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1200\/JCO.2013.50.4357","article-title":"Clinical utility of a plasma-based miRNA signature classifier within computed tomography lung cancer screening: A correlative MILD trial study","volume":"32","author":"Sozzi","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.annonc.2022.01.008","article-title":"Baseline computed tomography screening and blood microRNA predict lung cancer risk and define adequate intervals in the BioMILD trial","volume":"33","author":"Pastorino","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Rijavec, E., Coco, S., Genova, C., Rossi, G., Longo, L., Grossi, F., Vanni, I., Cera, D., Bottino, D., and Sini, M. (2020). Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges. Cancers, 12.","DOI":"10.3390\/cancers12010017"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Kan, C.F.K., Unis, G.D., Li, L.Z., Chan, D., and Cheng, C. (2021). Circulating biomarkers for early-stage non-small cell lung carcinoma detection: Supplementation to low-dose computed tomography. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.555331"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12943-020-1141-9","article-title":"Circulating tumor cells in cancer patients: Developments and clinical applications for immunotherapy","volume":"19","author":"Zhong","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Kapeleris, J., Ebrahimi Warkiani, M., Kulasinghe, A., Vela, I., Kenny, L., Ladwa, R., and O\u2019Byrne, K. (2022). Clinical applications of circulating tumour cells and circulating tumour DNA in non-small cell lung cancer\u2014An update. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.859152"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Kulasinghe, A., Lim, Y., Kapeleris, J., Warkiani, M., O\u2019Byrne, K., and Punyadeera, C. (2020). The use of three-dimensional DNA fluorescent in situ hybridization (3D DNA FISH) for the detection of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC) circulating tumor cells. Cells, 9.","DOI":"10.3390\/cells9061465"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41392-021-00817-8","article-title":"Circulating tumor cells: Biology and clinical significance","volume":"6","author":"Lin","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/s41571-023-00781-y","article-title":"Circulating tumour cells for early detection of clinically relevant cancer","volume":"20","author":"Lawrence","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Ju, S., Chen, C., Zhang, J., Lin, J., Jin, Z., Yan, P., Sun, Y., Li, Y., and Liu, B. (2022). Detection of circulating tumor cells: Opportunities and challenges. Biomark. Res., 10.","DOI":"10.1186\/s40364-022-00403-2"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Kulasinghe, A., Kapeleris, J., Cooper, C., Warkiani, M.E., O\u2019Byrne, K., and Punyadeera, C. (2019). Phenotypic characterization of circulating lung cancer cells for clinically actionable targets. Cancers, 11.","DOI":"10.3390\/cancers11030380"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Ilie, M., Hofman, V., Long-Mira, E., Selva, E., Vignaud, J.-M., Padovani, B., Frelin, C., Butori, C., Mouroux, J., and Poudenx, M. (2014). \u201cSentinel\u201d circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111597"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s10555-025-10247-5","article-title":"Minimally invasive biomarkers for triaging lung nodules-challenges and future perspectives","volume":"44","author":"Afridi","year":"2025","journal-title":"Cancer Metastasis Rev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3435","DOI":"10.21873\/anticanres.14329","article-title":"Clinical utility of combined circulating tumor cell and circulating tumor DNA assays for diagnosis of primary lung cancer","volume":"40","author":"Moon","year":"2020","journal-title":"Anticancer Res."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"De Luca, A., Gallo, M., Esposito, C., Morabito, A., and Normanno, N. (2021). Promising Role of Circulating Tumor Cells in the Management of SCLC. Cancers, 13.","DOI":"10.3390\/cancers13092029"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Wang, X., Bai, L., Kong, L., and Guo, Z. (2024). Advances in circulating tumor cells for early detection, prognosis and metastasis reduction in lung cancer. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1411731"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.molonc.2015.12.002","article-title":"Challenges in circulating tumor cell detection by the Cell Search system","volume":"10","author":"Andree","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.2147\/OTT.S241956","article-title":"Circulating Tumor Cells as a Screening and Diagnostic Marker for Early-Stage Non-Small Cell Lung Cancer","volume":"13","author":"Duan","year":"2020","journal-title":"OncoTargets Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.acc.2020.06.006","article-title":"Exosomes in cancer","volume":"101","author":"Bark","year":"2021","journal-title":"Adv. Clin. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"118623","DOI":"10.1016\/j.lfs.2020.118623","article-title":"Exosomes: A new horizon in modern medicine","volume":"264","author":"Deb","year":"2021","journal-title":"Life Sci."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Rajput, A., Varshney, A., Bajaj, R., and Pokharkar, V. (2022). Exosomes as New Generation Vehicles for Drug Delivery: Biomedical Applications and Future Perspectives. Molecules, 27.","DOI":"10.3390\/molecules27217289"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Kalluri, R., and LeBleu, V.S. (2020). The biology, function, and biomedical applications of exosomes. Science, 367.","DOI":"10.1126\/science.aau6977"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/j.jprot.2010.06.006","article-title":"Exosomes: Extracellular organelles important in intercellular communication","volume":"73","author":"Mathivanan","year":"2010","journal-title":"J. Proteom."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13045-015-0181-x","article-title":"Exosomes in cancer: Small particle, big player","volume":"8","author":"Zhang","year":"2015","journal-title":"J. Hematol. Oncol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"485","DOI":"10.2147\/CMAR.S232383","article-title":"Combination of Serum miRNAs with Serum Exosomal miRNAs in Early Diagnosis for Non-Small-Cell Lung Cancer","volume":"12","author":"Wu","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"5311","DOI":"10.1158\/1078-0432.CCR-17-0577","article-title":"Evaluation of tumor-derived exosomal miRNA as potential diagnostic biomarkers for early-stage non-small cell lung cancer using next-generation sequencing","volume":"3","author":"Jin","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, Y., Yin, Y., and Li, S. (2019). Detection of circulating exosomal miR-17-5p serves as a novel non-invasive diagnostic marker for non-small cell lung cancer patients. Pathol. Res. Pract., 215.","DOI":"10.1016\/j.prp.2019.152466"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"669","DOI":"10.3892\/ol.2016.5462","article-title":"Plasma miR-145, miR-20a, miR-21 and miR-223 as novel biomarkers for screening early-stage non-small cell lung cancer","volume":"13","author":"Zhang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.1007\/s13277-014-2938-1","article-title":"Serum miR-152, miR-148a, miR-148b, and miR-21 as novel biomarkers in non-small cell lung cancer screening","volume":"36","author":"Yang","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s41556-018-0066-7","article-title":"GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability","volume":"20","author":"Hu","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cell.2018.01.011","article-title":"Functional classification and experimental dissection of long noncoding RNAs","volume":"172","author":"Kopp","year":"2018","journal-title":"Cell"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"20721","DOI":"10.1002\/jcp.28678","article-title":"Tumor-derived exosomal lncRNA GAS5 as a biomarker for early-stage non-small-cell lung cancer diagnosis","volume":"234","author":"Li","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s40291-024-00715-z","article-title":"Diagnostic accuracy of exosomal long noncoding RNAs in diagnosis of NSCLC: A meta-analysis","volume":"28","author":"Song","year":"2024","journal-title":"Mol. Diagn. Ther."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Kang, Y., You, J., Gan, Y., Chen, Q., Huang, C., Chen, F., Xu, X., and Chen, L. (2022). Serum and Serum Exosomal CircRNAs hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 as Diagnostic Biomarkers for Lung Adenocarcinoma. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.912246"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.7150\/ijbs.66770","article-title":"CircRAPGEF5 Promotes the Proliferation and Metastasis of Lung Adenocarcinoma through the miR-1236-3p\/ ZEB1 Axis and Serves as a Potential Biomarker","volume":"18","author":"Zhou","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"153659","DOI":"10.1016\/j.prp.2021.153659","article-title":"Exosomal circ_0048856 derived from non-small cell lung cancer contributes to aggressive cancer progression through downregulation of miR-1287-5p","volume":"232","author":"He","year":"2022","journal-title":"Pathol. Res. Pract."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Huang, Y., Qin, S., Gu, X., Zheng, M., Zhang, Q., Liu, Y., Cheng, C., Huang, K., Peng, C., and Ju, S. (2021). Comprehensive assessment of serum hsa_circ_0070354 as a novel diagnostic and predictive biomarker in non-small cell lung cancer. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.796776"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.jmoldx.2020.05.011","article-title":"Identification of three circular RNA cargoes in serum exosomes as diagnostic biomarkers of non-small-cell lung cancer in the Chinese population","volume":"22","author":"Xian","year":"2020","journal-title":"J. Mol. Diagn."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.clinbiochem.2022.01.005","article-title":"Serum exosomal hsa_circ_0069313 has a potential to diagnose more aggressive non-small cell lung cancer","volume":"102","author":"Chen","year":"2022","journal-title":"Clin. Biochem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12943-017-0706-8","article-title":"Role of exosomal proteins in cancerdiagnosis","volume":"16","author":"Li","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"330","DOI":"10.3109\/07357907.2013.789905","article-title":"Epidermal growth factor receptorcontaining exosomes induce tumor-specific regulatory T cells","volume":"31","author":"Huang","year":"2013","journal-title":"Cancer Investig."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.7150\/jca.24601","article-title":"ADAM10 sheddase activity is a potential lung-cancer biomarker","volume":"9","author":"Yoneyama","year":"2018","journal-title":"J. Cancer"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/s12967-019-2101-2","article-title":"Clinical significance of PDL1 expression in serum-derived exosomes in NSCLC patients","volume":"17","author":"Li","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Choi, E.-S., Al Faruque, H., Kim, J.-H., Kim, K.J., Choi, J.E., Kim, B.A., Kim, B., Kim, Y.J., Woo, M.H., and Park, J.Y. (2021). CD5L as an extracellular vesicle-derived biomarker for liquid biopsy of lung cancer. Diagnostics, 11.","DOI":"10.3390\/diagnostics11040620"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1016\/j.jtho.2016.05.034","article-title":"Exosomal proteins as diagnostic biomarkers in lung cancer","volume":"11","author":"Jakobsen","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Ueda, K., Ishikawa, N., Tatsuguchi, A., Saichi, N., Fujii, R., and Nakagawa, H. (2014). Antibodycoupled monolithic silica microtips for high throughput molecular profiling of circulating exosomes. Sci. Rep., 4.","DOI":"10.1038\/srep06232"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Jeong, H., Choi, B.H., Park, J., Jung, J.H., Shin, H., Kang, K.W., Lee, D.G., and Kim, H.J. (2021). GCC2 as a new early diagnostic biomarker for non-small cell lung cancer. Cancers, 13.","DOI":"10.3390\/cancers13215482"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/cas.13862","article-title":"Tumor-derived exosomal proteins as diagnostic biomarkers in non-small cell lung cancer","volume":"110","author":"Niu","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1002\/elps.201000598","article-title":"Proteomic identification of exosomal LRG1: A potential urinary biomarker for detecting NSCLC","volume":"32","author":"Li","year":"2011","journal-title":"Electrophoresis"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Jin, S., Liu, T., Wang, W., Li, T., Liu, Z., and Zhang, M. (2023). Lymphocyte migration regulation related proteins in urine exosomes may serve as a potential biomarker for lung cancer diagnosis. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11567-x"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Sun, Y., Xia, Z., Shang, Z., Sun, K., Niu, X., Qian, L., Liu, S., Zhang, S., Cheng, Z., and Hu, G. (2016). Facile preparation of salivary extracellular vesicles for cancer proteomics. Sci. Rep., 6.","DOI":"10.1038\/srep24669"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1021\/acs.jproteome.7b00770","article-title":"Comparative proteomic analysis of exosomes and microvesicles in human saliva for lung cancer","volume":"17","author":"Sun","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.lungcan.2017.12.012","article-title":"Exosomes as a liquid biopsy for lung cancer","volume":"116","author":"Cui","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Zhao, J., Li, X., Liu, L., Zhu, Z., and He, C. (2023). Exosomes in lung cancer metastasis, diagnosis, and immunologically relevant advances. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1326667"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"6214","DOI":"10.18632\/aging.202504","article-title":"Early diagnosis of lung cancer: Which is the optimal choice?","volume":"13","author":"Ning","year":"2021","journal-title":"Aging"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Sun, Y., Fang, L., Yi, Y., Feng, A., Zhang, K., and Xu, J.J. (2022). Multistage nucleic acid amplification induced nano-aggregation for 3D hotspots-improved SERS detection of circulating miRNAs. J. Nanobiotechnol., 20.","DOI":"10.1186\/s12951-022-01500-y"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s13046-023-02753-7","article-title":"Exosome nanovesicles as potential biomarkers and immune checkpoint signaling modulators in lung cancer microenvironment: Recent advances and emerging concepts","volume":"42","author":"Khan","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"10712","DOI":"10.1021\/acsnano.7b04878","article-title":"The exosome total isolation chip","volume":"11","author":"Liu","year":"2017","journal-title":"ACS Nano"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.1182\/blood.2019003978","article-title":"Platelets and tumor-associated RNA transfer","volume":"137","author":"Nilsson","year":"2021","journal-title":"Blood"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1158\/0008-5472.CAN-18-0887","article-title":"Tumor-educated platelets as a noninvasive biomarker source for Cancer detection and progression monitoring","volume":"78","author":"Best","year":"2018","journal-title":"Cancer Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13046-024-03026-7","article-title":"Liquid biopsy techniques and lung cancer: Diagnosis, monitoring and evaluation","volume":"43","author":"Ren","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_165","first-page":"579","article-title":"Platelet RNA enables accurate detection of ovarian cancer: An intercontinental, biomarker identification study","volume":"14","author":"Gao","year":"2023","journal-title":"Protein Cell"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"102863","DOI":"10.1016\/j.critrevonc.2020.102863","article-title":"Tumor-educated platelet as liquid biopsy in lung cancer patients","volume":"146","author":"Liu","year":"2020","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12943-015-0327-z","article-title":"MicroRNA-223 delivered by platelet-derived microvesicles promotes lung cancer cell invasion via targeting tumor suppressor EPB41L3","volume":"14","author":"Liang","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Dong, X., Ding, S., Yu, M., Niu, L., Xue, L., Zhao, Y., Xie, L., Song, X., and Song, X. (2020). Small nuclear RNAs (U1, U2, U5) in tumor-educated platelets are downregulated and act as promising biomarkers in lung cancer. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01627"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ccell.2017.07.004","article-title":"Swarm intelligence-enhanced detection of non-small-cell lung cancer using tumor-educated platelets","volume":"32","author":"Best","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"8143","DOI":"10.2147\/OTT.S177384","article-title":"Identification of tumor-educated platelet biomarkers of non-small-cell lung cancer","volume":"11","author":"Sheng","year":"2018","journal-title":"Oncol. Targets Ther."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Li, D., Yang, W., Zhang, Y., Yang, J.Y., Guan, R., Xu, D., and Yang, M.Q. (2018). Genomic analyses based on pulmonary adenocarcinoma in situ reveal early lung cancer signature. BMC Med. Genom., 11.","DOI":"10.1186\/s12920-018-0413-3"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"3090","DOI":"10.21037\/tlcr-2025-747","article-title":"Tumor-educated platelet RNA as a diagnostic biomarker for ground-glass opacity-related lung adenocarcinoma","volume":"14","author":"Shao","year":"2025","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.7150\/ijbs.36284","article-title":"Development and validation of tumor-educated blood platelets integrin alpha 2b (ITGA2B) RNA for diagnosis and prognosis of non-small-cell lung cancer through RNA-seq","volume":"15","author":"Xing","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Antunes-Ferreira, M., D\u2019Ambrosi, S., Arkani, M., Post, E., In \u2018t Veld, S.G.J.G., Ramaker, J., van Leeuwen, T.H., van den Berg, R., Hahmann, L., and Wurdinger, T. (2023). Tumor-educated platelet blood tests for Non-Small Cell Lung Cancer detection and management. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-35818-w"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.ccell.2015.09.018","article-title":"RNA-Seq of tumor-educated platelets enables blood-based pan cancer, multiclass, and molecular pathway cancer diagnostics","volume":"28","author":"Best","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"120307","DOI":"10.1016\/j.cca.2025.120307","article-title":"Tumor-educated platelets in lung cancer","volume":"573","author":"Hussain","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.ccell.2018.03.002","article-title":"The platelet lifeline to cancer: Challenges and opportunities","volume":"33","author":"Haemmerle","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Sun, Y., Liu, R., Xia, X., Xing, L., Jiang, J., Bian, W., Zhang, W., Wang, C., and Zhang, C. (2022). Large-scale profiling on lncRNAs in human platelets: Correlation with platelet reactivity. Cells, 11.","DOI":"10.3390\/cells11142256"},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Lomnytska, M., Pinto, R., Becker, S., Engstr\u00f6m, U., Gustafsson, S., Bj\u00f6rklund, C., Templin, M., Bergstrand, J., Xu, L., and Widengren, J. (2018). Platelet protein biomarker panel for ovarian cancer diagnosis. Biomark Res., 6.","DOI":"10.1186\/s40364-018-0118-y"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s12935-023-02927-5","article-title":"Tumor educated platelet: The novel BioSource for cancer detection","volume":"23","author":"Ding","year":"2023","journal-title":"Cancer Cell Int."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Kannampuzha, S., Mukherjee, A.G., Wanjari, U.R., Gopalakrishnan, A.V., Murali, R., Namachivayam, A., Renu, K., Dey, A., Vellingiri, B., and Madhyastha, H. (2023). A Systematic Role of Metabolomics, Metabolic Pathways, and Chemical Metabolism in Lung Cancer. Vaccines, 11.","DOI":"10.3390\/vaccines11020381"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/978-981-10-6020-5_11","article-title":"Metabolic Changes During Cancer Cachexia Pathogenesis","volume":"1026","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Zhou, X., Tian, C., Cao, Y., Zhao, M., and Wang, K. (2022). The role of serine metabolism in lung cancer: From oncogenesis to tumor treatment. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.1084609"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"63437","DOI":"10.18632\/oncotarget.11521","article-title":"Non-targeted and targeted metabolomics approaches to diagnosing lung cancer and predicting patient prognosis","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"12904","DOI":"10.18632\/oncotarget.7354","article-title":"Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer","volume":"7","author":"Lucas","year":"2016","journal-title":"Oncotarget"},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Schult, T.A., Lauer, M.J., Berker, Y., Cardoso, M.R., Vandergrift, L.A., Habbel, P., Nowak, J., Taupitz, M., Aryee, M., and Mino-Kenudson, M.A. (2021). Screening human lung cancer with predictive models of serum magnetic resonance spectroscopy metabolomics. Proc. Natl. Acad. Sci. USA, 118.","DOI":"10.1073\/pnas.2110633118"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s11306-016-0961-5","article-title":"Temporal characterization of serum metabolite signatures in lung cancer patients undergoing treatment","volume":"12","author":"Hao","year":"2016","journal-title":"Metabolomics"},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"Musharraf, S.G., Mazhar, S., Choudhary, M.I., Rizi, N., and Rahman, A.U. (2015). Plasma metabolite profiling and chemometric analyses of lung cancer along with three controls through gas chromatography-mass spectrometry. Sci. Rep., 5.","DOI":"10.1038\/srep08607"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.36922\/td.2061","article-title":"Volatile organic compounds: A promising new frontier for cancer screening","volume":"3","author":"Singh","year":"2024","journal-title":"Tumor Discov."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Janfaza, S., Khorsand, B., Nikkhah, M., and Zahiri, J. (2019). Digging deeper into volatile organic compounds associated with cancer. Biol. Methods Protoc., 4.","DOI":"10.1093\/biomethods\/bpz014"},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Hanna, G.B., Boshier, P.R., Markar, S.R., and Romano, A. (2019). Accuracy and methodologic challenges of volatile organic compound based exhaled breath tests for cancer diagnosis: A systematic review and meta-analysis. JAMA Oncol., 5.","DOI":"10.1001\/jamaoncol.2018.2815"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1128\/CMR.00020-13","article-title":"Clinical application of volatile organic compound analysis for detecting infectious diseases","volume":"26","author":"Sethi","year":"2013","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"200","DOI":"10.4161\/cbt.26723","article-title":"Blood volatile compounds as biomarkers for colorectal cancer","volume":"15","author":"Wang","year":"2014","journal-title":"Cancer Biol. Ther."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.1007\/s00216-018-1103-x","article-title":"Screening of salivary volatiles for putative breast cancer discrimination: An exploratory study involving geographically distant populations","volume":"410","author":"Cavaco","year":"2018","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"026009","DOI":"10.1088\/1752-7163\/ab5b3c","article-title":"Investigation of sweat VOC profiles in assessment of cancer biomarkers using HS-GC-MS","volume":"14","author":"Monedeiro","year":"2020","journal-title":"J. Breath Res."},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Bajo-Fernandez, M., Souza-Silva, E.A., Barbas, C., Rey-Stolle, M.F., and Garcia, A. (2023). GC-MS-based metabolomics of volatile organic compounds in exhaled breath: Applications in health and disease. A review. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1295955"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Hara, T., Meng, S., Arao, Y., Saito, Y., Inoue, K., Alshammari, A.H., Hatakeyama, H., di Luccio, E., Vecchione, A., and Hirotsu, T. (2025). Non-Invasive Detection of Tumors by Volatile Organic Compounds in Urine. Biomedicines, 13.","DOI":"10.3390\/biomedicines13010109"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"404","DOI":"10.7150\/jca.4956","article-title":"Advances in gas chromatographic methods for the identification of biomarkers in cancer","volume":"3","author":"Kouremenos","year":"2012","journal-title":"J. Cancer"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.aca.2018.01.069","article-title":"Evolution of clinical and environmental health applications of exhaled breath research: Review of methods and instrumentation for gas-phase, condensate, and aerosols","volume":"1024","author":"Wallace","year":"2018","journal-title":"Anal. Chim. Acta"},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Baldini, C., Billeci, L., Sansone, F., Conte, R., Domenici, C., and Tonacci, A. (2020). Electronic nose as a novel method for diagnosing cancer: A systematic review. Biosensors, 10.","DOI":"10.3390\/bios10080084"},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Chen, K., Liu, L., Nie, B., Lu, B., Fu, L., He, Z., Li, W., Pi, X., and Liu, H. (2021). Recognizing lung cancer and stages using a self-developed electronic nose system. Comput. Biol. Med., 131.","DOI":"10.1016\/j.compbiomed.2021.104294"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"190002","DOI":"10.1183\/16000617.0002-2019","article-title":"Breath analysis of cancer in the present and the future","volume":"28","author":"Nakhleh","year":"2019","journal-title":"Eur. Respir. Rev."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Vassilenko, V., Moura, P.C., and Raposo, M. (2023). Diagnosis of Carcinogenic Pathologies through Breath Biomarkers: Present and Future Trends. Biomedicines, 11.","DOI":"10.3390\/biomedicines11113029"},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"Tsou, P.H., Lin, Z.L., Pan, Y.C., Yang, H.C., Chang, C.J., Liang, S.K., Wen, Y.F., Chang, C.H., Chang, L.Y., and Yu, K.L. (2021). Exploring Volatile Organic Compounds in Breath for High-Accuracy Prediction of Lung Cancer. Cancers, 13.","DOI":"10.3390\/cancers13061431"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"016007","DOI":"10.1088\/1752-7155\/10\/1\/016007","article-title":"Volatile signature for the early diagnosis of lung cancer","volume":"10","author":"Gasparri","year":"2016","journal-title":"J. Breath. Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"7355","DOI":"10.3390\/curroncol29100578","article-title":"The Use of Breath Analysis in the Management of Lung Cancer: Is It Ready for Primetime?","volume":"29","author":"Keogh","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"024002","DOI":"10.1088\/1752-7163\/acb791","article-title":"A review on electronic nose for diagnosis and monitoring treatment response in lung cancer","volume":"17","author":"Vadala","year":"2023","journal-title":"J. Breath Res."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1021\/acssensors.4c01524","article-title":"Nose-on-Chip Nanobiosensors for Early Detection of Lung Cancer Breath Biomarkers","volume":"9","author":"Chaudhary","year":"2024","journal-title":"ACS Sens."},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Su, Z., Yu, X., He, Y., Sha, T., Guo, H., Tao, Y., Liao, L., Zhang, Y., Lu, G., and Lu, G. (2024). Inconsistencies in predictive models based on exhaled volatile organic compounds for distinguishing between benign pulmonary nodules and lung cancer: A systematic review. BMC Pulm. Med., 24.","DOI":"10.1186\/s12890-024-03374-2"},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Fan, X., Zhong, R., Liang, H., Zhong, Q., Huang, H., He, J., Chen, Y., Wang, Z., Xie, S., and Jiang, Y. (2024). Exhaled VOC detection in lung cancer screening: A comprehensive meta-analysis. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12537-7"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s11306-024-02142-x","article-title":"Progress and challenges of developing volatile metabolites from exhaled breath as a biomarker platform","volume":"20","author":"Chou","year":"2024","journal-title":"Metabolomics"},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Jia, Z., Jiang, Y., Shang, T., Cao, H., Li, J., Cong, L., Pu, P., Xu, H., Liu, Y., and Huang, Y. (2025). Advanced strategy for cancer detection based on volatile organic compounds in breath. J. Nanobiotechnol., 23.","DOI":"10.1186\/s12951-025-03526-4"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"198","DOI":"10.4103\/mgr.MEDGASRES-D-24-00101","article-title":"Non-invasive detection of early-stage lung cancer through exhaled breath volatile organic compound analysis","volume":"15","author":"Binson","year":"2024","journal-title":"Med. Gas Res."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s11633-019-1212-9","article-title":"Electronic Nose and Its Applications: A Survey","volume":"17","author":"Karakaya","year":"2020","journal-title":"Int. J. Autom. Comput."},{"key":"ref_215","doi-asserted-by":"crossref","unstructured":"Scheepers, M., Al-Difaie, Z., Brandts, L., Peeters, A., van Grinsven, B., and Bouvy, N.D. (2022). Diagnostic Performance of Electronic Noses in Cancer Diagnoses Using Exhaled Breath: A Systematic Review and Meta-analysis. JAMA Netw. Open, 5.","DOI":"10.1001\/jamanetworkopen.2022.19372"},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Kanan, M., Alharbi, H., Alotaibi, N., Almutairi, N., Albishi, H., Alshammari, A., Alzahrani, A., Alyami, N., Alanazi, A., and Alqahtani, F. (2024). Ai-driven models for diagnosing and predicting outcomes in lung cancer: A systematic review and meta-analysis. Cancers, 16.","DOI":"10.3390\/cancers16030674"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/clinchem\/hvad196","article-title":"Looking to the Future of Early Detection in Cancer: Liquid Biopsies, Imaging, and Artificial Intelligence","volume":"70","author":"Foser","year":"2024","journal-title":"Clin. Chem."},{"key":"ref_218","doi-asserted-by":"crossref","unstructured":"Peters, A.A., Wiescholek, N., M\u00fcller, M., Brix, M., Booz, C., Kellersmann, J., Peters, J., and Peters, E.N. (2024). Impact of artificial intelligence assistance on pulmonary nodule detection and localization in chest CT: A comparative study among radiologists of varying experience levels. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-73435-3"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jtho.2023.07.019","article-title":"Current and Future Perspectives on Computed Tomography Screening for Lung Cancer: A Roadmap From 2023 to 2027 From the International Association for the Study of Lung Cancer","volume":"19","author":"Lam","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"W52","DOI":"10.1097\/RTI.0000000000000698","article-title":"Automated Coronary Artery Calcium and Quantitative Emphysema in Lung Cancer Screening: Association with Mortality, Lung Cancer Incidence, and Airflow Obstruction","volume":"38","author":"Balbi","year":"2023","journal-title":"J. Thorac. Imaging"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/s43856-023-00388-5","article-title":"Deep learning for the detection of benign and malignant pulmonary nodules in non-screening chest CT scans","volume":"3","author":"Hendrix","year":"2023","journal-title":"Commun. Med."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"100481","DOI":"10.1016\/j.ejro.2023.100481","article-title":"Simultaneous assessment of heart and lungs with gated high-pitch ultra-low dose chest CT using artificial intelligence-based calcium scoring","volume":"10","author":"Andre","year":"2023","journal-title":"Eur. J. Radiol. Open"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"3444","DOI":"10.1007\/s00330-023-10348-1","article-title":"Influence of CT dose reduction on AI-driven malignancy estimation of incidental pulmonary nodules","volume":"34","author":"Peters","year":"2023","journal-title":"Eur. Radiol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.diii.2021.12.002","article-title":"Impact of dose reduction and iterative reconstruction algorithm on the detectability of pulmonary nodules by artificial intelligence","volume":"103","author":"Schwyzer","year":"2022","journal-title":"Diagn. Interv. Imaging"},{"key":"ref_225","doi-asserted-by":"crossref","unstructured":"Zhao, K., Jiang, B., Zhang, S., Zhang, L., Zhang, L., Feng, Y., Li, J., Zhang, Y., and Xie, X. (2022). Measurement Accuracy and Repeatability of RECIST-Defined Pulmonary Lesions and Lymph Nodes in Ultra-Low-Dose CT Based on Deep Learning Image Reconstruction. Cancers, 14.","DOI":"10.3390\/cancers14205016"},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Ziegelmayer, S., Graf, M., Makowski, M., Gawlitza, J., and Gassert, F. (2022). Cost-Effectiveness of Artificial Intelligence Support in Computed Tomography-Based Lung Cancer Screening. Cancers, 14.","DOI":"10.3390\/cancers14071729"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"3130","DOI":"10.1111\/1759-7714.14140","article-title":"Predictive value of a novel Asian lung cancer screening nomogram based on artificial intelligence and epidemiological characteristics","volume":"12","author":"Liu","year":"2021","journal-title":"Thorac. Cancer"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"9840","DOI":"10.18632\/aging.103249","article-title":"Development of a machine learning-based multimode diagnosis system for lung cancer","volume":"12","author":"Duan","year":"2020","journal-title":"Aging"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jtho.2023.08.016","article-title":"The International Association for the Study of Lung Cancer Early Lung Imaging Confederation Open-Source Deep Learning and Quantitative Measurement Initiative","volume":"19","author":"Lam","year":"2024","journal-title":"J. Thorac. Oncol."},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Simon, J., Mikhael, P., Tahir, I., Graur, A., Ringer, S., Fata, A., Jeffrey, Y.C., Shepard, J.A., Jacobson, F., and Barzilay, R. (2023). Role of sex in lung cancer risk prediction based on single low-dose chest computed tomography. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-45671-6"},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Wang, G., Qiu, M., Xing, X., Zhou, J., Yao, H., Li, M., Yin, R., Hou, Y., Li, Y., and Pan, S. (2022). Lung cancer scRNA-seq and lipidomics reveal aberrant lipid metabolism for early-stage diagnosis. Sci. Transl. Med., 14.","DOI":"10.1126\/scitranslmed.abk2756"},{"key":"ref_232","doi-asserted-by":"crossref","unstructured":"Yang, H., Chen, H., Zhang, G., Li, H., Ni, R., Yu, Y., Zhang, Y., Wu, Y., and Liu, H. (2022). Diagnostic value of circulating genetically abnormal cells to support computed tomography for benign and malignant pulmonary nodules. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09472-w"},{"key":"ref_233","doi-asserted-by":"crossref","unstructured":"Bahado-Singh, R., Vlachos, K.T., Aydas, B., Gordevicius, J., Radhakrishna, U., and Vishweswaraiah, S. (2022). Precision Oncology: Artificial Intelligence and DNA Methylation Analysis of Circulating Cell-Free DNA for Lung Cancer Detection. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.790645"},{"key":"ref_234","unstructured":"American College of Radiology (2025, August 26). ACR Lung Cancer Screening CT Incidental Findings. Available online: https:\/\/thoracicrad.org\/wp-content\/uploads\/2021\/11\/ACR-LCS-IF-one-pager.pdf."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1016\/j.chest.2021.12.662","article-title":"Standardizing the reporting of incidental, non-lung cancer (category S) findings identified on lung cancer screening low-dose CT imaging","volume":"161","author":"Tanoue","year":"2022","journal-title":"Chest"},{"key":"ref_236","doi-asserted-by":"crossref","unstructured":"Kim, M., Park, J., Oh, S., Jeong, B.-H., Byun, Y., Shin, S.H., Im, Y., Cho, J.H., and Cho, E.-H. (2024). Deep learning model integrating cfDNA methylation and fragment size profiles for lung cancer diagnosis. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-63411-2"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1186\/s12967-023-04663-w","article-title":"Deep neural network-based tissue deconvolution of circulating tumor cell RNA","volume":"21","author":"Yan","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_238","doi-asserted-by":"crossref","unstructured":"Vinhas, M., Leit\u00e3o, P.M., Raimundo, B.S., Gil, N., Vaz, P.D., and Luis-Ferreira, F. (2024). AI Applied to Volatile Organic Compound (VOC) Profiles from Exhaled Breath Air for Early Detection of Lung Cancer. Cancers, 16.","DOI":"10.3390\/cancers16122200"},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Raimundo, B.S., Leit\u00e3o, P.M., Vinhas, M., Pires, M.V., Quintas, L.B., Carvalheiro, C., Barata, R., Ip, J., Coelho, R., and Granadeiro, S. (2025). Breath Insights: Advancing Lung Cancer Early-Stage Detection Through AI Algorithms in Non-Invasive VOC Profiling Trials. Cancers, 17.","DOI":"10.3390\/cancers17101685"},{"key":"ref_240","doi-asserted-by":"crossref","unstructured":"Chamouni, G., Lococo, F., Sassorossi, C., Atuhaire, N., \u00c1d\u00e1ny, R., and Varga, O. (2025). Ethical and legal concerns in artificial intelligence applications for the diagnosis and treatment of lung cancer: A scoping review. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1663298"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"102769","DOI":"10.1016\/j.eclinm.2024.102769","article-title":"Development and validation of an integrated system for lung cancer screening and post-screening pulmonary nodules management: A proof-of-concept study (ASCEND-LUNG)","volume":"75","author":"Jin","year":"2024","journal-title":"eClinicalMedicine"},{"key":"ref_242","doi-asserted-by":"crossref","unstructured":"Duranti, L., Tavecchio, L., Rolli, L., and Solli, P. (2025). New Perspectives on Lung Cancer Screening and Artificial Intelligence. Life, 15.","DOI":"10.3390\/life15030498"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s10238-025-01752-6","article-title":"Innovative technologies and their clinical prospects for early lung cancer screening","volume":"25","author":"Deng","year":"2025","journal-title":"Clin. Exp. Med."},{"key":"ref_244","doi-asserted-by":"crossref","unstructured":"Huang, D., Li, Z., Jiang, T., Yang, C., and Li, N. (2024). Artificial intelligence in lung cancer: Current applications, future perspectives, and challenges. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1486310"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s44174-023-00063-2","article-title":"Drawbacks of Artificial Intelligence and Their Potential Solutions in the Healthcare Sector","volume":"1","author":"Khan","year":"2023","journal-title":"Biomed. Mater. Devices"},{"key":"ref_246","doi-asserted-by":"crossref","unstructured":"Mehraeen, E., Siami, H., Montazeryan, S., Molavi, R., Feyzabadi, A., Parvizy, I., Masjedlu, Z.A., Dehkalani, M.N., Mahmoudi, S., and Ahmadipour, A. (2025). Artificial Intelligence Challenges in the Healthcare Industry: A Systematic Review of Recent Evidence. Healthc. Technol. Lett., 12.","DOI":"10.1049\/htl2.70017"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1071\/HC24035","article-title":"Primary care clinicians should proactively take up latest AI-based technology: Yes","volume":"16","year":"2024","journal-title":"J. Prim. Health Care"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"100933","DOI":"10.1016\/j.xcrm.2023.100933","article-title":"Integration of artificial intelligence in lung cancer: Rise of the machine","volume":"4","author":"Ladbury","year":"2023","journal-title":"Cell Rep. Med."},{"key":"ref_249","doi-asserted-by":"crossref","unstructured":"Cellina, M., Cacioppa, L.M., C\u00e8, M., Chiarpenello, V., Costa, M., Vincenzo, Z., Pais, D., Bausano, M.V., Rossini, N., and Bruno, A. (2023). Artificial Intelligence in Lung Cancer Screening: The Future Is Now. Cancers, 15.","DOI":"10.3390\/cancers15174344"},{"key":"ref_250","first-page":"303","article-title":"The future of multimodal artificial intelligence models for integrating imaging and clinical metadata: A narrative review","volume":"31","author":"Simon","year":"2024","journal-title":"Diagn. Interv. Radiol."},{"key":"ref_251","doi-asserted-by":"crossref","unstructured":"Gandhi, Z., Gurram, P., Amgai, B., Lekkala, S.P., Lokhandwala, A., Manne, S., Mohammed, A., Koshiya, H., Dewaswala, N., and Desai, R. (2023). Artificial Intelligence and Lung Cancer: Impact on Improving Patient Outcomes. Cancers, 15.","DOI":"10.3390\/cancers15215236"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7812\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T19:56:22Z","timestamp":1762199782000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":251,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["jcm14217812"],"URL":"https:\/\/doi.org\/10.3390\/jcm14217812","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]}}}