{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T08:48:41Z","timestamp":1793522921106,"version":"4.5.0"},"reference-count":216,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Early cancer detection remains a central challenge in oncology because many lethal tumors are diagnosed after curative opportunities have narrowed, whereas current organ-specific screening methods cover only a limited number of cancer types and may be constrained by invasiveness, cost, accessibility or stage-dependent sensitivity. Liquid biopsy, multi-cancer early detection (MCED) and artificial intelligence (AI) are rapidly reshaping this field, but their clinical implications require careful interpretation. This review critically evaluates major liquid-biopsy analytes, including circulating tumor DNA, cell-free DNA methylation and fragmentomics, circulating tumor cells, extracellular vesicles, non-coding RNAs, tumor-educated platelets and multi-omics signatures, with emphasis on intended use, clinical maturity, tissue-of-origin value and translational limitations. A distinctive feature of this review is the integration of tumor-derived signals with host-response and immunological readouts, including peripheral blood mononuclear cell-based monitoring, immune-cell-derived extracellular vesicles, exosomal immune-checkpoint molecules and inflammatory confounders, thereby framing liquid biopsy as both a cancer-detection tool and a window into tumor\u2013immune interactions. We further discuss MCED as a clinical care pathway rather than an isolated blood test, highlighting the importance of positive and negative predictive values, cancer prevalence, diagnostic-resolution pathways, false-positive workup, overdiagnosis, mortality benefit, cost-effectiveness and equitable access. The role of AI is examined in relation to model development, multimodal fusion, tissue-of-origin prediction, calibration, interpretability, bias, generalizability and clinical implementation. Across these technologies, a key translational message is that technical detectability is not equivalent to clinical readiness. While selected assays have entered defined clinical or guideline-supported settings, many emerging biomarkers and AI-enabled models remain investigational or translational. Future progress will depend on standardized workflows, prospective validation in representative populations, evidence of clinical utility, regulatory and ethical oversight, and integration with established screening and diagnostic systems.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1854718","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T05:39:08Z","timestamp":1781588348000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Liquid biopsy, multi-cancer early detection, and artificial intelligence: new frontiers in cancer screening from a technological and immunological perspective"],"prefix":"10.3389","volume":"17","author":[{"given":"Dong","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Fuyang People\u2019s Hospital","place":["Fuyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tongling People\u2019s Hospital, Tongling Academy of Medical Sciences","place":["Tongling, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province; School of Pharmaceutical Sciences, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Fuyang People\u2019s Hospital","place":["Fuyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojie","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Fuyang People\u2019s Hospital","place":["Fuyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Fuyang Cancer Hospital","place":["Fuyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Fuyang People\u2019s Hospital","place":["Fuyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second People\u2019s Hospital of Fuyang City, Fuyang Infectious Disease Clinical College of Anhui Medical University","place":["Fuyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Fuyang People\u2019s Hospital","place":["Fuyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","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":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(25)01570-3","article-title":"Global cancer burden: progress, projections, and challenges","volume":"406","author":"Luo","year":"2025","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.43198","article-title":"Global disparities of cancer and its projected burden in 2050","volume":"7","author":"Bizuayehu","year":"2024","journal-title":"JAMA Netw Open"},{"key":"B4","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.34944","article-title":"Differences in survival and recurrence of colorectal cancer by stage across population-based European registries","volume":"155","author":"Bouvier","year":"2024","journal-title":"Int J Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2014.11.002","article-title":"Screening for cancer: when to stop?: A practical guide and review of the evidence","volume":"99","author":"Soung","year":"2015","journal-title":"Med Clin North Am"},{"key":"B7","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1186\/s40001-025-03003-6","article-title":"Emerging biomarkers for early cancer detection and diagnosis: challenges, innovations, and clinical perspectives","volume":"30","author":"Zafar","year":"2025","journal-title":"Eur J Med Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2023.154812","article-title":"Biomarkers and biosensors for early cancer diagnosis, monitoring and prognosis","volume":"250","author":"Wahab","year":"2023","journal-title":"Pathol Res Pract"},{"key":"B9","article-title":"Clinical significance of preoperative serum CEA and CA 19-9 level in different stages of gastric cancer","volume":"34","author":"Sharif","year":"2025","journal-title":"Mymensingh Med J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2024.06.003","article-title":"Prostate-specific antigen screening for prostate cancer: diagnostic performance, clinical thresholds, and strategies for refinement","volume":"43","author":"Sundaresan","year":"2025","journal-title":"Urol Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0272308","article-title":"Sensitivity and specificity of microRNA-204, CA125, and CA19.9 as biomarkers for diagnosis of ovarian cancer","volume":"17","author":"Ali","year":"2022","journal-title":"PloS One"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13061386","article-title":"Comparative study of elevated CA19-9 levels in non-gastrointestinal tumors patients: evaluation of different immunoassay methods and analysis of potential interfering factors","volume":"13","author":"Liu","year":"2025","journal-title":"Biomedicines"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2024.106588","article-title":"PSA, an outdated biomarker for prostate cancer: in search of a more specific biomarker, citrate takes the spotlight","volume":"243","author":"Galey","year":"2024","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B14","first-page":"1","article-title":"An overview of liquid biopsy for screening and early detection of cancer","volume-title":"CADTH Issues in Emerging Health Technologies","author":"Cowling","year":"2019"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlb.2024.100146","article-title":"Liquid biopsy into the clinics: current evidence and future perspectives","volume":"4","author":"Boukovala","year":"2024","journal-title":"J Liq Biopsy"},{"key":"B16","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/bs.acc.2017.10.003","article-title":"Liquid biopsy: from basic research to clinical practice","volume":"83","author":"Mac\u00edas","year":"2018","journal-title":"Adv Clin Chem"},{"key":"B17","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/s41698-024-00568-z","article-title":"A multi-cancer early detection blood test using machine learning detects early-stage cancers lacking USPSTF-recommended screening","volume":"8","author":"Vittone","year":"2024","journal-title":"NPJ Precis Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(23)01700-2","article-title":"Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study","volume":"402","author":"Schrag","year":"2023","journal-title":"Lancet"},{"key":"B19","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s12943-025-02369-9","article-title":"Current AI technologies in cancer diagnostics and treatment","volume":"24","author":"Tiwari","year":"2025","journal-title":"Mol Cancer"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbaf440","article-title":"Deep learning-driven multi-omics analysis: enhancing cancer diagnostics and therapeutics","volume":"26","author":"Zhang","year":"2025","journal-title":"Brief Bioinform"},{"key":"B21","doi-asserted-by":"publisher","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":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11081391","article-title":"Liquid biopsy: a family of possible diagnostic tools","volume":"11","author":"Michela","year":"2021","journal-title":"Diagn (Basel)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2023.117674","article-title":"Liquid biopsy in colorectal cancer","volume":"553","author":"Najafi","year":"2024","journal-title":"Clin Chim Acta"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/cas.16097","article-title":"Beyond blood: Advancing the frontiers of liquid biopsy in oncology and personalized medicine","volume":"115","author":"Bao","year":"2024","journal-title":"Cancer Sci"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12040809","article-title":"PBMCs as Tool for identification of novel immunotherapy biomarkers in lung cancer","volume":"12","author":"De Rosa","year":"2024","journal-title":"Biomedicines"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-06-1695","article-title":"Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system","volume":"13","author":"Riethdorf","year":"2007","journal-title":"Clin Cancer Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/617421","article-title":"Significance of circulating tumor cells detected by the CellSearch system in patients with metastatic breast colorectal and prostate cancer","volume":"2010","author":"Miller","year":"2010","journal-title":"J Oncol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s40291-020-00473-8","article-title":"Epi proColon\u00ae for colorectal cancer screening: a profile of its use in the USA","volume":"24","author":"Shirley","year":"2020","journal-title":"Mol Diagn Ther"},{"key":"B29","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/s41391-021-00456-8","article-title":"Predicting high-grade prostate cancer at initial biopsy: clinical performance of the ExoDx (EPI) Prostate Intelliscore test in three independent prospective studies","volume":"25","author":"Margolis","year":"2022","journal-title":"Prostate Cancer Prostatic Dis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1272-6","article-title":"Genome-wide cell-free DNA fragmentation in patients with cancer","volume":"570","author":"Cristiano","year":"2019","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/j.ccell.2022.08.006","article-title":"Detection and localization of early- and late-stage cancers using platelet RNA","volume":"40","author":"In 't Veld","year":"2022","journal-title":"Cancer Cell"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J Extracell Vesicles"},{"key":"B33","doi-asserted-by":"publisher","first-page":"224ra24","DOI":"10.1126\/scitranslmed.3007094","article-title":"Detection of circulating tumor DNA in early- and late-stage human Malignancies","volume":"6","author":"Bettegowda","year":"2014","journal-title":"Sci Transl Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2024.101258","article-title":"Circulating tumor cells as liquid biopsy markers in cancer patients","volume":"96","author":"Smit","year":"2024","journal-title":"Mol Aspects Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2024-0959","article-title":"Clinical applications of circulating tumor cell detection: challenges and strategies","volume":"63","author":"Ma","year":"2024","journal-title":"Clin Chem Lab Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlb.2025.100307","article-title":"Novel applications of liquid Biopsy: Comprehensive methodology for circulating biomarker exploration in peripheral blood","volume":"9","author":"De Rosa","year":"2025","journal-title":"J Liq Biopsy"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-025-00795-x","article-title":"Genomic and fragmentomic landscapes of cell-free DNA for early cancer detection","volume":"25","author":"Bruhm","year":"2025","journal-title":"Nat Rev Cancer"},{"key":"B38","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ejca.2022.10.015","article-title":"Methylation biomarkers for early cancer detection and diagnosis: Current and future perspectives","volume":"178","author":"Ibrahim","year":"2023","journal-title":"Eur J Cancer"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2304714","article-title":"A cell-free DNA blood-based test for colorectal cancer screening","volume":"390","author":"Chung","year":"2024","journal-title":"N Engl J Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2025.105106","article-title":"Tumor-educated platelets as liquid biopsy: Uncovering the mechanisms of cancer progression","volume":"218","author":"Schmidl","year":"2026","journal-title":"Crit Rev Oncol Hematol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics15172216","article-title":"Interpretable multi-cancer early detection using SHAP-based machine learning on tumor-educated platelet RNA","volume":"15","author":"Hajjar","year":"2025","journal-title":"Diagn (Basel)"},{"key":"B42","doi-asserted-by":"publisher","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":"B43","doi-asserted-by":"publisher","DOI":"10.1080\/17501911.2025.2467021","article-title":"Circulating non-coding RNAs as a tool for liquid biopsy in solid tumors","volume":"17","author":"Karaca Dogan","year":"2025","journal-title":"Epigenomics"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncrna.2024.06.015","article-title":"Exploring the role of noncoding RNAs in cancer diagnosis, prognosis, and precision medicine","volume":"9","author":"Eldakhakhny","year":"2024","journal-title":"Non-coding RNA Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.82","article-title":"Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis","volume":"25","author":"Li","year":"2015","journal-title":"Cell Res"},{"key":"B46","doi-asserted-by":"publisher","first-page":"22136","DOI":"10.1038\/s41598-024-73783-0","article-title":"Noninvasive multi-cancer detection using blood-based cell-free microRNAs","volume":"14","author":"Zhang","year":"2024","journal-title":"Sci Rep"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-024-02706-7","article-title":"Graph machine learning for integrated multi-omics analysis","volume":"131","author":"Valous","year":"2024","journal-title":"Br J Cancer"},{"key":"B48","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1186\/s13059-024-03401-9","article-title":"Assessing and mitigating batch effects in large-scale omics studies","volume":"25","author":"Yu","year":"2024","journal-title":"Genome Biol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar3247","article-title":"Detection and localization of surgically resectable cancers with a multi-analyte blood test","volume":"359","author":"Cohen","year":"2018","journal-title":"Science"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12082277","article-title":"Clonal hematopoiesis in liquid biopsy: from biological noise to valuable clinical implications","volume":"12","author":"Chan","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B51","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41698-021-00202-2","article-title":"Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA","volume":"5","author":"Finkle","year":"2021","journal-title":"NPJ Precis Oncol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.05.806","article-title":"Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set","volume":"32","author":"Klein","year":"2021","journal-title":"Ann Oncol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.02.011","article-title":"Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA","volume":"31","author":"Liu","year":"2020","journal-title":"Ann Oncol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-22-0659","article-title":"Detecting liver cancer using cell-free DNA fragmentomes","volume":"13","author":"Foda","year":"2023","journal-title":"Cancer Discov"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01672-8","article-title":"Non-coding RNAs as liquid biopsy biomarkers in cancer","volume":"126","author":"Toden","year":"2022","journal-title":"Br J Cancer"},{"key":"B56","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41698-022-00283-7","article-title":"Blood-derived lncRNAs as biomarkers for cancer diagnosis: the Good, the Bad and the Beauty","volume":"6","author":"Badowski","year":"2022","journal-title":"NPJ Precis Oncol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2013.00094","article-title":"The impact of hemolysis on cell-free microRNA biomarkers","volume":"4","author":"Kirschner","year":"2013","journal-title":"Front Genet"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2023.03.005","article-title":"Preanalytic methodological considerations and sample quality control of circulating miRNAs","volume":"25","author":"Chan","year":"2023","journal-title":"J Mol Diagn"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/cbm-210223","article-title":"Circulating microRNAs: Challenges with their use as liquid biopsy biomarkers","volume":"35","author":"Takizawa","year":"2022","journal-title":"Cancer biomark"},{"key":"B60","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s13040-024-00391-z","article-title":"Deep learning-based approaches for multi-omics data integration and analysis","volume":"17","author":"Ballard","year":"2024","journal-title":"Biodata Min"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.202400100","article-title":"Computational methods for data integration and imputation of missing values in omics datasets","volume":"25","author":"Schumann","year":"2025","journal-title":"Proteomics"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical Bayes methods","volume":"8","author":"Johnson","year":"2007","journal-title":"Biostatistics"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01934-1","article-title":"Multi-omics data integration using ratio-based quantitative profiling with Quartet reference materials","volume":"42","author":"Zheng","year":"2024","journal-title":"Nat Biotechnol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1016\/j.ccell.2024.07.005","article-title":"Integrative plasma and fecal metabolomics identify functional metabolites in adenoma-colorectal cancer progression and as early diagnostic biomarkers","volume":"42","author":"Sun","year":"2024","journal-title":"Cancer Cell"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1559480","article-title":"Microbiota as diagnostic biomarkers: advancing early cancer detection and personalized therapeutic approaches through microbiome profiling","volume":"16","author":"Eslami","year":"2025","journal-title":"Front Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26846","article-title":"Droplet digital PCR of viral DNA\/RNA, current progress, challenges, and future perspectives","volume":"93","author":"Kojabad","year":"2021","journal-title":"J Med Virol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.2144\/99261rv01","article-title":"Quantitative RT-PCR: pitfalls and potential","volume":"26","author":"Freeman","year":"1999","journal-title":"Biotechniques"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6730-8_8","article-title":"Multiplex analyses using real-time quantitative PCR","volume":"1546","author":"Hawkins","year":"2017","journal-title":"Methods Mol Biol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.4103\/jpbs.jpbs_838_23","article-title":"Next-generation sequencing (NGS): platforms and applications","volume":"16","author":"Mandlik","year":"2024","journal-title":"J Pharm Bioallied Sci"},{"key":"B70","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s13045-020-01005-x","article-title":"RNA sequencing: new technologies and applications in cancer research","volume":"13","author":"Hong","year":"2020","journal-title":"J Hematol Oncol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-025-02648-9","article-title":"Error-corrected flow-based sequencing at whole-genome scale and its application to circulating cell-free DNA profiling","volume":"22","author":"Cheng","year":"2025","journal-title":"Nat Methods"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01108-x","article-title":"Nanopore sequencing technology, bioinformatics and applications","volume":"39","author":"Wang","year":"2021","journal-title":"Nat Biotechnol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0703-0","article-title":"Sensitive tumour detection and classification using plasma cell-free DNA methylomes","volume":"563","author":"Shen","year":"2018","journal-title":"Nature"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8973-7_11","article-title":"Quantitative methylation-specific PCR: a simple method for studying epigenetic modifications of cell-free DNA","volume":"1909","author":"Sigalotti","year":"2019","journal-title":"Methods Mol Biol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186466","article-title":"A review of exosomal isolation methods: is size exclusion chromatography the best option","volume":"21","author":"Sidhom","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.811971","article-title":"Review on strategies and technologies for exosome isolation and purification","volume":"9","author":"Chen","year":"2022","journal-title":"Front Bioeng Biotechnol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13050970","article-title":"A review of circulating tumour cell enrichment technologies","volume":"13","author":"Rushton","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B78","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.molonc.2015.12.002","article-title":"Challenges in circulating tumor cell detection by the CellSearch system","volume":"10","author":"Andree","year":"2016","journal-title":"Mol Oncol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17223638","article-title":"Integrating multi-omics and medical imaging in artificial intelligence-based cancer research: an umbrella review of fusion strategies and applications","volume":"17","author":"Marouf","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B80","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.cytogfr.2024.08.006","article-title":"Biomarker discovery in hepatocellular carcinoma (HCC) for personalized treatment and enhanced prognosis","volume":"79","author":"Yu","year":"2024","journal-title":"Cytokine Growth Factor Rev"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12983","article-title":"Mutated circulating tumor DNA as a liquid biopsy in lung cancer detection and treatment","volume":"15","author":"Filipska","year":"2021","journal-title":"Mol Oncol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2025.0002","article-title":"NCCN guidelines\u00ae insights: lung cancer screening, Version 1.2025","volume":"23","author":"Wood","year":"2025","journal-title":"J Natl Compr Canc Netw"},{"key":"B83","doi-asserted-by":"publisher","first-page":"497","DOI":"10.6004\/jnccn.2022.0025","article-title":"Non-small cell lung cancer, Version 3.2022, NCCN clinical practice guidelines in oncology","volume":"20","author":"Ettinger","year":"2022","journal-title":"J Natl Compr Canc Netw"},{"key":"B84","doi-asserted-by":"publisher","first-page":"4953","DOI":"10.1038\/s41467-022-32598-1","article-title":"Genome-wide mutational signatures in low-coverage whole genome sequencing of cell-free DNA","volume":"13","author":"Wan","year":"2022","journal-title":"Nat Commun"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180647","article-title":"Assessment of circulating copy number variant detection for cancer screening","volume":"12","author":"Molparia","year":"2017","journal-title":"PloS One"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbac200","article-title":"A computational framework to unify orthogonal information in DNA methylation and copy number aberrations in cell-free DNA for early cancer detection","volume":"23","author":"Wei","year":"2022","journal-title":"Brief Bioinform"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00078","article-title":"Circulating cell-free DNA in hepatocellular carcinoma: current insights and outlook","volume":"5","author":"Ng","year":"2018","journal-title":"Front Med (Lausanne)"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.18632\/aging.205980","article-title":"Circulating tumor DNA mutation analysis: advances in its application for early diagnosis of hepatocellular carcinoma and therapeutic efficacy monitoring","volume":"16","author":"Yang","year":"2024","journal-title":"Aging (Albany NY)"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13092274","article-title":"Liquid biopsy in hepatocellular carcinoma: where are we now","volume":"13","author":"Pelizzaro","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B90","doi-asserted-by":"publisher","first-page":"28705","DOI":"10.1038\/s41598-024-77781-0","article-title":"Bladder cancer detection in urine by novel methylation markers","volume":"14","author":"Beijert","year":"2024","journal-title":"Sci Rep"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1111\/bju.14673","article-title":"Diagnostic accuracy, clinical utility and influence on decision-making of a methylation urine biomarker test in the surveillance of non-muscle-invasive bladder cancer","volume":"123","author":"D'Andrea","year":"2019","journal-title":"BJU Int"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2018.06.011","article-title":"Performance of the bladder EpiCheck\u2122 methylation test for patients under surveillance for non-muscle-invasive bladder cancer: results of a multicenter, prospective, blinded clinical trial","volume":"1","author":"Witjes","year":"2018","journal-title":"Eur Urol Oncol"},{"key":"B93","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/s41523-021-00316-7","article-title":"Circulating cell-free DNA-based methylation patterns for breast cancer diagnosis","volume":"7","author":"Zhang","year":"2021","journal-title":"NPJ Breast Cancer"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30534","article-title":"Performance of a new HPV and biomarker assay in the management of hrHPV positive women: Subanalysis of the ongoing multicenter TRACE clinical trial (n\u2009>\u20096,000) to evaluate POU4F3 methylation as a potential biomarker of cervical precancer and cancer","volume":"140","author":"Kocsis","year":"2017","journal-title":"Int J Cancer"},{"key":"B95","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1186\/s12916-024-03662-y","article-title":"Evaluation of a plasma cell-free DNA methylation test for colorectal cancer diagnosis: a multicenter clinical study","volume":"22","author":"Wang","year":"2024","journal-title":"BMC Med"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1172\/jci186816","article-title":"A multicenter prospective clinical trial reveals cell-free DNA methylation markers for early esophageal cancer","volume":"135","author":"Zhang","year":"2025","journal-title":"J Clin Invest"},{"key":"B97","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/s12943-025-02367-x","article-title":"GUIDE: a prospective cohort study for blood-based early detection of gastrointestinal cancers using targeted DNA methylation and fragmentomics sequencing","volume":"24","author":"Huang","year":"2025","journal-title":"Mol Cancer"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30244","article-title":"Hepatocellular carcinoma detection by plasma methylated DNA: discovery, phase I pilot, and phase II clinical validation","volume":"69","author":"Kisiel","year":"2019","journal-title":"Hepatology"},{"key":"B99","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.1016\/j.cgh.2020.08.065","article-title":"A novel blood-based panel of methylated DNA and protein markers for detection of early-stage hepatocellular carcinoma","volume":"19","author":"Chalasani","year":"2021","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1038\/nmat4997","article-title":"Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma","volume":"16","author":"Xu","year":"2017","journal-title":"Nat Mater"},{"key":"B101","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s13148-023-01508-7","article-title":"HepaClear, a blood-based panel combining novel methylated CpG sites and protein markers, for the detection of early-stage hepatocellular carcinoma","volume":"15","author":"Bai","year":"2023","journal-title":"Clin Epigenet"},{"key":"B102","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.jtho.2016.08.123","article-title":"Validation of the SHOX2\/PTGER4 DNA methylation marker panel for plasma-based discrimination between patients with Malignant and nonmalignant lung disease","volume":"12","author":"Weiss","year":"2017","journal-title":"J Thorac Oncol"},{"key":"B103","doi-asserted-by":"publisher","first-page":"2002682","DOI":"10.1183\/13993003.02682-2020","article-title":"Validation of Lung EpiCheck, a novel methylation-based blood assay, for the detection of lung cancer in European and Chinese high-risk individuals","volume":"57","author":"Gaga","year":"2021","journal-title":"Eur Respir J"},{"key":"B104","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.1038\/s41467-020-17316-z","article-title":"Non-invasive early detection of cancer four years before conventional diagnosis using a blood test","volume":"11","author":"Chen","year":"2020","journal-title":"Nat Commun"},{"key":"B105","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1016\/j.annonc.2021.08.765","article-title":"Evaluation of cell-free DNA approaches for multi-cancer early detection","volume":"40","author":"Jamshidi","year":"2022","journal-title":"Cancer Cell"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw3616","article-title":"Epigenetics, fragmentomics, and topology of cell-free DNA in liquid biopsies","volume":"372","author":"Lo","year":"2021","journal-title":"Science"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12040978","article-title":"Cell-free DNA fragmentomics in liquid biopsy","volume":"12","author":"Ding","year":"2022","journal-title":"Diagn (Basel)"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.09.006","article-title":"Cell-free DNA fragmentomics in cancer","volume":"43","author":"Tsui","year":"2025","journal-title":"Cancer Cell"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abm6863","article-title":"Genome-wide analysis of aberrant position and sequence of plasma DNA fragment ends in patients with cancer","volume":"15","author":"Budhraja","year":"2023","journal-title":"Sci Transl Med"},{"key":"B110","doi-asserted-by":"publisher","first-page":"8801","DOI":"10.1016\/j.annonc.2024.08.073","article-title":"Cancer treatment monitoring using cell-free DNA fragmentomes","volume":"15","author":"van 't Erve","year":"2024","journal-title":"Nat Commun"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-25-0074","article-title":"Detection of brain cancer using genome-wide cell-free DNA fragmentomes","volume":"15","author":"Mathios","year":"2025","journal-title":"Cancer Discov"},{"key":"B112","doi-asserted-by":"publisher","first-page":"5060","DOI":"10.1038\/s41467-021-24994-w","article-title":"Detection and characterization of lung cancer using cell-free DNA fragmentomes","volume":"12","author":"Mathios","year":"2021","journal-title":"Nat Commun"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-24-0393","article-title":"Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers","volume":"15","author":"Medina","year":"2025","journal-title":"Cancer Discov"},{"key":"B114","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1186\/s12916-024-03531-8","article-title":"Early detection of uterine corpus endometrial carcinoma utilizing plasma cfDNA fragmentomics","volume":"22","author":"Liu","year":"2024","journal-title":"BMC Med"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14679","article-title":"Fragmentation of cell-free DNA is induced by upper-tract urothelial carcinoma-associated systemic inflammation","volume":"112","author":"Nakano","year":"2021","journal-title":"Cancer Sci"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2022.100242","article-title":"Circulating DNA fragmentomics and cancer screening","volume":"3","author":"Thierry","year":"2023","journal-title":"Cell Genom"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvaa196","article-title":"Breast cancer detection and treatment monitoring using a noninvasive prenatal testing platform: utility in pregnant and nonpregnant populations","volume":"66","author":"Lenaerts","year":"2020","journal-title":"Clin Chem"},{"key":"B118","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12916-016-0667-6","article-title":"Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening","volume":"14","author":"Cohen","year":"2016","journal-title":"BMC Med"},{"key":"B119","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/nature17038","article-title":"Metastatic colonization by circulating tumour cells","volume":"529","author":"Massagu\u00e9","year":"2016","journal-title":"Nature"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1183\/13993003\/erj.38.suppl_55.4506","article-title":"Sentinel\" circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease","volume":"9","author":"Ilie","year":"2014","journal-title":"PloS One"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14143341","article-title":"Accurate screening for early-stage breast cancer by detection and profiling of circulating tumor cells","volume":"14","author":"Crook","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.5649","article-title":"Accurate prostate cancer detection based on enrichment and characterization of prostate cancer specific circulating tumor cells","volume":"12","author":"Limaye","year":"2023","journal-title":"Cancer Med"},{"key":"B123","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1097\/ju.0000000000000475","article-title":"Noninvasive detection of clinically significant prostate cancer using circulating tumor cells","volume":"203","author":"Xu","year":"2020","journal-title":"J Urol"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000088","article-title":"Novel circulating tumor cell assay for detection of colorectal adenomas and cancer","volume":"10","author":"Tsai","year":"2019","journal-title":"Clin Transl Gastroenterol"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-023-02435-6","article-title":"Diagnosis of colorectal cancer based on folate receptor-positive circulating tumor cell analysis: a retrospective cohort study","volume":"29","author":"Wei","year":"2024","journal-title":"Int J Clin Oncol"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.4172\/2472-0429.1000123","article-title":"Screening for circulating tumour cells allows early detection of cancer and monitoring of treatment effectiveness: an observational study","volume":"18","author":"Ried","year":"2017","journal-title":"Asian Pac J Cancer Prev"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-2600(20)30081-3","article-title":"Circulating tumour cells as a potential biomarker for lung cancer screening: a prospective cohort study","volume":"8","author":"Marquette","year":"2020","journal-title":"Lancet Respir Med"},{"key":"B128","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1038\/s41467-023-37403-1","article-title":"Single test-based diagnosis of multiple cancer types using Exosome-SERS-AI for early stage cancers","volume":"14","author":"Shin","year":"2023","journal-title":"Nat Commun"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.3c00929","article-title":"Encoded fusion-mediated microRNA signature profiling of tumor-derived extracellular vesicles for pancreatic cancer diagnosis","volume":"95","author":"Feng","year":"2023","journal-title":"Anal Chem"},{"key":"B130","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s12943-025-02271-4","article-title":"Identification of blood-derived exosomal tumor RNA signatures as noninvasive diagnostic biomarkers for multi-cancer: a multi-phase, multi-center study","volume":"24","author":"Wang","year":"2025","journal-title":"Mol Cancer"},{"key":"B131","doi-asserted-by":"publisher","first-page":"RP88675","DOI":"10.2139\/ssrn.4405690","article-title":"Circulating small extracellular vesicle RNA profiling for the detection of T1a stage colorectal cancer and precancerous advanced adenoma","volume":"12","author":"Min","year":"2024","journal-title":"Elife"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1039\/d4sc05518g","article-title":"A simplified and efficient extracellular vesicle-based proteomics strategy for early diagnosis of colorectal cancer","volume":"15","author":"Zhang","year":"2024","journal-title":"Chem Sci"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1097117","article-title":"Circulating exosomal immuno-oncological checkpoints and cytokines are potential biomarkers to monitor tumor response to anti-PD-1\/PD-L1 therapy in non-small cell lung cancer patients","volume":"13","author":"Akbar","year":"2023","journal-title":"Front Immunol"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16183151","article-title":"Immune-cell-derived exosomes as a potential novel tool to investigate immune responsiveness in SCLC patients: a proof-of-concept study","volume":"16","author":"Amato","year":"2024","journal-title":"Cancers (Basel)"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100164","article-title":"The molecular profiling of solid tumors by liquid biopsy: a position paper of the AIOM-SIAPEC-IAP-SIBioC-SIC-SIF Italian Scientific Societies","volume":"6","author":"Russo","year":"2021","journal-title":"ESMO Open"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12156","article-title":"Role of platelets in inflammation and cancer: novel therapeutic strategies","volume":"114","author":"Dovizio","year":"2014","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-019-0139-5","article-title":"RNA sequencing and swarm intelligence-enhanced classification algorithm development for blood-based disease diagnostics using spliced blood platelet RNA","volume":"14","author":"Best","year":"2019","journal-title":"Nat Protoc"},{"key":"B138","doi-asserted-by":"publisher","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":"B139","doi-asserted-by":"publisher","DOI":"10.3390\/cells11142256","article-title":"Large-scale profiling on lncRNAs in human platelets: correlation with platelet reactivity","volume":"11","author":"Sun","year":"2022","journal-title":"Cells"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.21129","article-title":"Assessment of the diagnostic efficiency of a liquid biopsy assay for early detection of gastric cancer","volume":"4","author":"Izumi","year":"2021","journal-title":"JAMA Netw Open"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2020.151642","article-title":"LncRNA PCAT6: A potential biomarker for diagnosis and prognosis of bladder cancer","volume":"49","author":"Zhang","year":"2020","journal-title":"Ann Diagn Pathol"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.21987","article-title":"Evaluation of the role of circulating long non-coding RNA H19 as a promising novel biomarker in plasma of patients with gastric cancer","volume":"30","author":"Hashad","year":"2016","journal-title":"J Clin Lab Anal"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9997212","article-title":"Serum-based lncRNA ANRIL, TUG1, UCA1, and HIT expressions in breast cancer patients","volume":"2022","author":"Alkhathami","year":"2022","journal-title":"Dis Markers"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.537120","article-title":"Circulating long noncoding RNAs act as diagnostic biomarkers in non-small cell lung cancer","volume":"10","author":"Yuan","year":"2020","journal-title":"Front Oncol"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000024805","article-title":"lncRNA-UCA1 in the diagnosis of bladder cancer: A meta-analysis","volume":"100","author":"Ding","year":"2021","journal-title":"Med (Baltimore)"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0177","article-title":"Association between combined TMPRSS2:ERG and PCA3 RNA urinary testing and detection of aggressive prostate cancer","volume":"3","author":"Sanda","year":"2017","journal-title":"JAMA Oncol"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2022.153800","article-title":"A review on the role of PCA3 lncRNA in carcinogenesis with an especial focus on prostate cancer","volume":"231","author":"Ghafouri-Fard","year":"2022","journal-title":"Pathol Res Pract"},{"key":"B148","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/dlmt1294","article-title":"Multi-cancer early detection tests for general population screening: a systematic literature review","volume":"29","author":"Wade","year":"2025","journal-title":"Health Technol Assess"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.epi-21-1387","article-title":"Multi-cancer early detection tests: current progress and future perspectives","volume":"31","author":"Loomans-Kropp","year":"2022","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abp8704","article-title":"Simultaneous analysis of mutations and methylations in circulating cell-free DNA for hepatocellular carcinoma detection","volume":"14","author":"Wang","year":"2022","journal-title":"Sci Transl Med"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104553","article-title":"Multi-omics integrated circulating cell-free DNA genomic signatures enhanced the diagnostic performance of early-stage lung cancer and postoperative minimal residual disease","volume":"91","author":"Li","year":"2023","journal-title":"Ebiomedicine"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1200\/po.24.00111","article-title":"Genome-scale multimodal analysis of cell-free DNA whole-methylome sequencing for noninvasive esophageal cancer detection","volume":"8","author":"Li","year":"2024","journal-title":"Jco Precis Oncol"},{"key":"B153","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/s12943-024-01959-3","article-title":"Integration of multiomics features for blood-based early detection of colorectal cancer","volume":"23","author":"Gao","year":"2024","journal-title":"Mol Cancer"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-022-02048-2","article-title":"Integrative analysis of multi-omics data for liquid biopsy","volume":"128","author":"Chen","year":"2023","journal-title":"Br J Cancer"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.3389\/frai.2024.1408843","article-title":"Multimodal data integration for oncology in the era of deep neural networks: a review","volume":"7","author":"Waqas","year":"2024","journal-title":"Front Artif Intell"},{"key":"B156","doi-asserted-by":"publisher","first-page":"bbaf355","DOI":"10.1093\/bib\/bbaf355","article-title":"A technical review of multi-omics data integration methods: from classical statistical to deep generative approaches","volume":"26","author":"Bai\u00e3o","year":"2025","journal-title":"Brief Bioinform"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2023.1152470","article-title":"Enhancing clinical potential of liquid biopsy through a multi-omic approach: a systematic review","volume":"14","author":"Di Sario","year":"2023","journal-title":"Front Genet"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1395332","article-title":"Exosomal PD-L1 in cancer and other fields: recent advances and perspectives","volume":"15","author":"Lu","year":"2024","journal-title":"Front Immunol"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.02.010","article-title":"Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies","volume":"34","author":"Gao","year":"2023","journal-title":"Ann Oncol"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.capr-23-0451","article-title":"Outcomes following a false-positive multi-cancer early detection test: results from DETECT-A, the first large, prospective, interventional MCED study","volume":"17","author":"Lennon","year":"2024","journal-title":"Cancer Prev Res (Phila)"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1177\/18758592241297849","article-title":"Multi-cancer early detection tests: attributes for clinical implementation","volume":"42","author":"Ebbert","year":"2025","journal-title":"Cancer biomark"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-025-01033-x","article-title":"Promises and pitfalls of multi-cancer early detection using liquid biopsy tests","volume":"22","author":"Wan","year":"2025","journal-title":"Nat Rev Clin Oncol"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.11.006","article-title":"Noninvasive detection and localization of genitourinary cancers using urinary sediment DNA methylomes and copy number profiles","volume":"77","author":"Xu","year":"2020","journal-title":"Eur Urol"},{"key":"B164","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/odi.13630","article-title":"Salivary LDH in oral cancer and potentially Malignant disorders: a systematic review and meta-analysis","volume":"28","author":"Iglesias-Vel\u00e1zquez","year":"2022","journal-title":"Oral Dis"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.02.005","article-title":"ctDNA detection in cerebrospinal fluid and plasma and mutational concordance with the primary tumor in a multicenter prospective study of patients with glioma","volume":"36","author":"Cabezas-Camarero","year":"2025","journal-title":"Ann Oncol"},{"key":"B166","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-21-1982","article-title":"EpiPanGI Dx: a cell-free DNA methylation fingerprint for the early detection of gastrointestinal cancers","volume":"27","author":"Kandimalla","year":"2021","journal-title":"Clin Cancer Res"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102053","article-title":"CAN-Scan: a multi-omic phenotype-driven precision oncology platform identifies prognostic biomarkers of therapy response for colorectal cancer","volume":"6","author":"Chia","year":"2025","journal-title":"Cell Rep Med"},{"key":"B168","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102041","article-title":"A panel of seven protein tumour markers for effective and affordable multi-cancer early detection by artificial intelligence: a large-scale and multicentre case-control study","volume":"61","author":"Luan","year":"2023","journal-title":"Eclinicalmedicine"},{"key":"B169","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb9601","article-title":"Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention","volume":"369","author":"Lennon","year":"2020","journal-title":"Science"},{"key":"B170","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.capr-24-0107","article-title":"Multiyear clinical outcomes of cancers diagnosed following detection by a blood-based multicancer early detection test","volume":"17","author":"Buchanan","year":"2024","journal-title":"Cancer Prev Res (Phila)"},{"key":"B171","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(24)00645-4","article-title":"Psychosocial impact associated with a multicancer early detection test (PATHFINDER): a prospective, multicentre, cohort study","volume":"26","author":"Nadauld","year":"2025","journal-title":"Lancet Oncol"},{"key":"B172","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(23)00277-2","article-title":"Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): a large-scale, observational cohort study","volume":"24","author":"Nicholson","year":"2023","journal-title":"Lancet Oncol"},{"key":"B173","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12916-025-03929-y","article-title":"Prospective validation study: a non-invasive circulating tumor DNA-based assay for simultaneous early detection of multiple cancers in asymptomatic adults","volume":"23","author":"Nguyen","year":"2025","journal-title":"BMC Med"},{"key":"B174","doi-asserted-by":"publisher","first-page":"6042","DOI":"10.1038\/s41467-023-41774-w","article-title":"Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization","volume":"14","author":"Bie","year":"2023","journal-title":"Nat Commun"},{"key":"B175","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.ccell.2024.04.008","article-title":"Comprehensive peripheral blood immunoprofiling reveals five immunotypes with immunotherapy response characteristics in patients with cancer","volume":"42","author":"Dyikanov","year":"2024","journal-title":"Cancer Cell"},{"key":"B176","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00298-X","article-title":"Artificial intelligence-supported screen reading versus standard double reading in the Mammography Screening with Artificial Intelligence trial (MASAI): a clinical safety analysis of a randomised, controlled, non-inferiority, single-blinded, screening accuracy study","volume":"24","author":"L\u00e5ng","year":"2023","journal-title":"Lancet Oncol"},{"key":"B177","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000020977","article-title":"Development of a deep learning-based automated diagnostic system (DLADS) for classifying mammographic lesions - a first large-scale multi-institutional clinical trial in Japan","volume":"32","author":"Yamaguchi","year":"2025","journal-title":"Breast Cancer"},{"key":"B178","doi-asserted-by":"publisher","DOI":"10.1136\/thorax-2023-220226","article-title":"Radiomics analysis to predict pulmonary nodule Malignancy using machine learning approaches","volume":"79","author":"Warkentin","year":"2024","journal-title":"Thorax"},{"key":"B179","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0447-x","article-title":"End-to-end lung cancer screening with three-dimensional deep learning on low-dose chest computed tomography","volume":"25","author":"Ardila","year":"2019","journal-title":"Nat Med"},{"key":"B180","doi-asserted-by":"publisher","first-page":"14797","DOI":"10.1038\/s41598-024-63411-2","article-title":"Deep learning model integrating cfDNA methylation and fragment size profiles for lung cancer diagnosis","volume":"14","author":"Kim","year":"2024","journal-title":"Sci Rep"},{"key":"B181","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101689","article-title":"Machine learning-based analysis identifies and validates serum exosomal proteomic signatures for the diagnosis of colorectal cancer","volume":"5","author":"Yin","year":"2024","journal-title":"Cell Rep Med"},{"key":"B182","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/s41698-024-00719-2","article-title":"Development and validation of machine learning models for young-onset colorectal cancer risk stratification","volume":"8","author":"Zhen","year":"2024","journal-title":"NPJ Precis Oncol"},{"key":"B183","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105183","article-title":"Deep learning for colorectal cancer detection in contrast-enhanced CT without bowel preparation: a retrospective, multicentre study","volume":"104","author":"Yao","year":"2024","journal-title":"Ebiomedicine"},{"key":"B184","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.232635","article-title":"Fully automated deep learning model to detect clinically significant prostate cancer at MRI","volume":"312","author":"Cai","year":"2024","journal-title":"Radiology"},{"key":"B185","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.232788","article-title":"MRI-based deep learning algorithm for assisting clinically significant prostate cancer detection: a bicenter prospective study","volume":"314","author":"Lee","year":"2025","journal-title":"Radiology"},{"key":"B186","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2025.112063","article-title":"Machine learning models for enhanced diagnosis and risk assessment of prostate cancer with 68Ga-PSMA-617 PET\/CT","volume":"186","author":"Zhu","year":"2025","journal-title":"Eur J Radiol"},{"key":"B187","doi-asserted-by":"publisher","DOI":"10.1186\/s12938-024-01219-x","article-title":"Screening ovarian cancer by using risk factors: machine learning assists","volume":"23","author":"Nopour","year":"2024","journal-title":"BioMed Eng Online"},{"key":"B188","doi-asserted-by":"publisher","first-page":"594","DOI":"10.3390\/life15040594","article-title":"Prediction of early diagnosis in ovarian cancer patients using machine learning approaches with boruta and advanced feature selection","volume":"15","author":"\u00d6znacar","year":"2025","journal-title":"Life (Basel)"},{"key":"B189","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.7163","article-title":"Bayesian and deep-learning models applied to the early detection of ovarian cancer using multiple longitudinal biomarkers","volume":"13","author":"Abrego","year":"2024","journal-title":"Cancer Med"},{"key":"B190","doi-asserted-by":"publisher","DOI":"10.1016\/s2589-7500(21)00278-8","article-title":"Deep learning-enabled pelvic ultrasound images for accurate diagnosis of ovarian cancer in China: a retrospective, multicentre, diagnostic study","volume":"4","author":"Gao","year":"2022","journal-title":"Lancet Digit Health"},{"key":"B191","doi-asserted-by":"publisher","first-page":"8392","DOI":"10.1038\/s41467-023-44255-2","article-title":"Proteomics-driven noninvasive screening of circulating serum protein panels for the early diagnosis of hepatocellular carcinoma","volume":"14","author":"Xing","year":"2023","journal-title":"Nat Commun"},{"key":"B192","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/s43856-024-00677-7","article-title":"Spatial omics-based machine learning algorithms for the early detection of hepatocellular carcinoma","volume":"4","author":"Wang","year":"2024","journal-title":"Commun Med (Lond)"},{"key":"B193","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1038\/s41746-025-01892-9","article-title":"AI enhanced diagnostic accuracy and workload reduction in hepatocellular carcinoma screening","volume":"8","author":"Lu","year":"2025","journal-title":"NPJ Digit Med"},{"key":"B194","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0311810","article-title":"Combining metabolomics and machine learning to discover biomarkers for early-stage breast cancer diagnosis","volume":"19","author":"Anh","year":"2024","journal-title":"PloS One"},{"key":"B195","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1038\/s41467-024-46043-y","article-title":"Metabolomic machine learning predictor for diagnosis and prognosis of gastric cancer","volume":"15","author":"Chen","year":"2024","journal-title":"Nat Commun"},{"key":"B196","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-078378","article-title":"TRIPOD+AI statement: updated guidance for reporting clinical prediction models that use regression or machine learning methods","volume":"385","author":"Collins","year":"2024","journal-title":"Bmj"},{"key":"B197","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2024-081554","article-title":"FUTURE-AI: international consensus guideline for trustworthy and deployable artificial intelligence in healthcare","volume":"388","author":"Lekadir","year":"2025","journal-title":"Bmj"},{"key":"B198","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/s41746-024-01270-x","article-title":"A scoping review of reporting gaps in FDA-approved AI medical devices","volume":"7","author":"Muralidharan","year":"2024","journal-title":"NPJ Digit Med"},{"key":"B199","doi-asserted-by":"publisher","DOI":"10.7326\/m18-1376","article-title":"PROBAST: a tool to assess the risk of bias and applicability of prediction model studies","volume":"170","author":"Moons","year":"2019","journal-title":"Ann Intern Med"},{"key":"B200","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03113-4","article-title":"The limits of fair medical imaging AI in real-world generalization","volume":"30","author":"Yang","year":"2024","journal-title":"Nat Med"},{"key":"B201","doi-asserted-by":"publisher","first-page":"8270","DOI":"10.1038\/s41467-024-52618-6","article-title":"Generalizability assessment of AI models across hospitals in a low-middle and high income country","volume":"15","author":"Yang","year":"2024","journal-title":"Nat Commun"},{"key":"B202","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pdig.0000651","article-title":"Bias in medical AI: Implications for clinical decision-making","volume":"3","author":"Cross","year":"2024","journal-title":"PloS Digit Health"},{"key":"B203","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m3164","article-title":"Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI extension","volume":"26","author":"Liu","year":"2020","journal-title":"Nat Med"},{"key":"B204","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m3210","article-title":"Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension","volume":"26","author":"Cruz Rivera","year":"2020","journal-title":"Nat Med"},{"key":"B205","doi-asserted-by":"publisher","DOI":"10.1148\/ryai.240300","article-title":"Checklist for artificial intelligence in medical imaging (CLAIM): 2024 update","volume":"6","author":"Tejani","year":"2024","journal-title":"Radiol Artif Intell"},{"key":"B206","doi-asserted-by":"publisher","DOI":"10.1017\/s0963180124000744","article-title":"Ethical considerations and implications of multi-cancer early detection screening: reliability, access and cost to test and treat","volume":"34","author":"Sempere","year":"2025","journal-title":"Camb Q Healthc Ethics"},{"key":"B207","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12910-024-01012-4","article-title":"Ethics of early detection of disease risk factors: A scoping review","volume":"25","author":"Jansen","year":"2024","journal-title":"BMC Med Ethics"},{"key":"B208","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2024.101270","article-title":"Ethical, legal, and social issues related to genetics and genomics in cancer: A scoping review and narrative synthesis","volume":"26","author":"Smit","year":"2024","journal-title":"Genet Med"},{"key":"B209","doi-asserted-by":"publisher","DOI":"10.1200\/po.23.00382","article-title":"Recommendations for the equitable and widespread implementation of liquid biopsy for cancer care","volume":"8","author":"Febbo","year":"2024","journal-title":"JCO Precis Oncol"},{"key":"B210","doi-asserted-by":"publisher","DOI":"10.1093\/haschl\/qxae039","article-title":"Multi-cancer early detection (MCED) tests: prioritizing equity from bench to bedside","volume":"2","author":"Miller","year":"2024","journal-title":"Health Aff Sch"},{"key":"B211","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1307459","article-title":"Integrating primary care, shared decision making, and community engagement to facilitate equitable access to multi-cancer early detection clinical trials","volume":"13","author":"Thompson","year":"2024","journal-title":"Front Oncol"},{"key":"B212","doi-asserted-by":"publisher","DOI":"10.1002\/cnr2.70176","article-title":"The cost-effectiveness of a multi-target stool DNA-based screening (COLOTECT), FIT, colonoscopy and no screening for colorectal cancer","volume":"8","author":"Huang","year":"2025","journal-title":"Cancer Rep (Hoboken)"},{"key":"B213","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.epi-24-1549","article-title":"Novel noninvasive tests for colorectal cancer screening - a cost-effectiveness analysis","volume":"34","author":"Rui","year":"2025","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B214","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202411945","article-title":"Cost-effective identification of hepatocellular carcinoma from cirrhosis or chronic hepatitis virus infection using eight methylated plasma DNA markers","volume":"12","author":"Yang","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"B215","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41416-023-02243-9","article-title":"Modelled mortality benefits of multi-cancer early detection screening in England","volume":"129","author":"Sasieni","year":"2023","journal-title":"Br J Cancer"},{"key":"B216","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.epi-25-0610","article-title":"Cost-effectiveness of a multicancer early detection test in the US","volume":"30","author":"Kansal","year":"2024","journal-title":"Am J Manag Care"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1854718\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T05:39:10Z","timestamp":1781588350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1854718\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":216,"alternative-id":["10.3389\/fimmu.2026.1854718"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1854718","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]},"article-number":"1854718"}}