{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T20:25:40Z","timestamp":1785443140198,"version":"3.56.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-73783-0","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T14:03:42Z","timestamp":1727445822000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Noninvasive multi-cancer detection using blood-based cell-free microRNAs"],"prefix":"10.1038","volume":"14","author":[{"given":"Jason","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hallgeir","family":"Rui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"73783_CR1","doi-asserted-by":"crossref","unstructured":"Sung, H. et al. Global Cancer Statistics: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin.71(3), 209\u2013249 (2021).","DOI":"10.3322\/caac.21660"},{"issue":"1","key":"73783_CR2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","volume":"72","author":"RL Siegel","year":"2022","unstructured":"Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin.72(1), 7\u201333 (2022).\u00a0","journal-title":"CA Cancer J. Clin."},{"key":"73783_CR3","doi-asserted-by":"crossref","unstructured":"Ahlquist, D. A. Universal cancer screening: revolutionary, rational, and realizable. NPJ Precis Oncol. 2, 23 (2018).","DOI":"10.1038\/s41698-018-0066-x"},{"key":"73783_CR4","unstructured":"Noone, A. M. et al. (eds) SEER Cancer Statistics Review, 1975\u20132015, National Cancer Institute. (2018)."},{"key":"73783_CR5","doi-asserted-by":"crossref","unstructured":"Siu, A. L. & U.S. Preventive Services Task Force. Screening for breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann. Intern. Med. 164 (4), 279\u2013296 (2016).","DOI":"10.7326\/M15-2886"},{"key":"73783_CR6","doi-asserted-by":"crossref","unstructured":"US Preventive Services Task Force et al. Screening for cervical Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 320(7), 674\u2013686 (2018).","DOI":"10.1001\/jama.2018.10897"},{"key":"73783_CR7","doi-asserted-by":"crossref","unstructured":"US Preventive Services Task Force et al. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 325(19), 1965\u20131977 (2021).","DOI":"10.1001\/jama.2021.6238"},{"key":"73783_CR8","doi-asserted-by":"crossref","unstructured":"US Preventive Services Task Force et al. Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 325(10), 962\u2013970 (2021).","DOI":"10.1001\/jama.2021.1117"},{"issue":"3","key":"73783_CR9","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1370\/afm.942","volume":"7","author":"JM Croswell","year":"2009","unstructured":"Croswell, J. M. et al. Cumulative incidence of false-positive results in repeated, multimodal cancer screening. Ann. Fam Med.7(3), 212\u2013222 (2009).","journal-title":"Ann. Fam Med."},{"issue":"6","key":"73783_CR10","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.3390\/cancers14061450","volume":"14","author":"A Zhang","year":"2022","unstructured":"Zhang, A. & Hu, H. A novel blood-based microRNA diagnostic model with high accuracy for Multi-cancer Early Detection. Cancers (Basel). 14(6), 1450 (2022).","journal-title":"Cancers (Basel)"},{"issue":"16_suppl","key":"73783_CR11","doi-asserted-by":"publisher","first-page":"3065","DOI":"10.1200\/JCO.2022.40.16_suppl.3065","volume":"40","author":"A Zhang","year":"2022","unstructured":"Zhang, A. & Hu, H. Independent validation of a novel noninvasive 4-microRNA diagnostic model for multicancer early detection. J. Clin. Oncol.40(16_suppl), 3065\u20133065 (2022).","journal-title":"J. Clin. Oncol."},{"key":"73783_CR12","doi-asserted-by":"crossref","unstructured":"Asakura, K. et al. A miRNA-based diagnostic model predicts resectable lung cancer in humans with high accuracy. Commun. Biol. 3(1), 134 (2020).","DOI":"10.1038\/s42003-020-0863-y"},{"key":"73783_CR13","doi-asserted-by":"crossref","unstructured":"Yokoi, A. et al. Integrated extracellular microRNA profiling for ovarian cancer screening. Nat. Commun. 9(1), 4319 (2018).","DOI":"10.1038\/s41467-018-06434-4"},{"issue":"2","key":"73783_CR14","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1002\/hep4.1451","volume":"4","author":"Y Yamamoto","year":"2020","unstructured":"Yamamoto, Y. et al. Highly sensitive circulating MicroRNA Panel for Accurate Detection of Hepatocellular Carcinoma in patients with Liver Disease. Hepatol. Commun. 4(2), 284\u2013297 (2020).","journal-title":"Hepatol. Commun."},{"key":"73783_CR15","doi-asserted-by":"crossref","unstructured":"Usuba, W. et al. Circulating miRNA panels for specific and early detection in bladder cancer. Cancer Sci. 110(1), 408\u2013419 (2019).","DOI":"10.1111\/cas.13856"},{"issue":"5","key":"73783_CR16","doi-asserted-by":"publisher","first-page":"e194573","DOI":"10.1001\/jamanetworkopen.2019.4573","volume":"2","author":"K Sudo","year":"2019","unstructured":"Sudo, K. et al. Development and validation of an esophageal squamous cell carcinoma detection model by large-scale MicroRNA profiling. JAMA Netw. Open.2(5), e194573 (2019).","journal-title":"JAMA Netw. Open."},{"issue":"4","key":"73783_CR17","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1007\/s10120-021-01161-0","volume":"24","author":"S Abe","year":"2021","unstructured":"Abe, S. et al. A novel combination of serum microRNAs for the detection of early gastric cancer. Gastric Cancer. 24(4), 835\u2013843 (2021).","journal-title":"Gastric Cancer"},{"issue":"12","key":"73783_CR18","doi-asserted-by":"publisher","first-page":"e1916953","DOI":"10.1001\/jamanetworkopen.2019.16953","volume":"2","author":"M Ohno","year":"2019","unstructured":"Ohno, M. et al. Assessment of the diagnostic utility of serum MicroRNA classification in patients with diffuse glioma. JAMA Netw. Open.2(12), e1916953 (2019).","journal-title":"JAMA Netw. Open."},{"issue":"10","key":"73783_CR19","doi-asserted-by":"publisher","first-page":"3016","DOI":"10.1158\/1078-0432.CCR-18-2849","volume":"25","author":"F Urabe","year":"2019","unstructured":"Urabe, F. et al. Large-scale circulating microRNA profiling for the liquid biopsy of prostate Cancer. Clin. Cancer Res.25(10), 3016\u20133025 (2019).","journal-title":"Clin. Cancer Res."},{"key":"73783_CR20","doi-asserted-by":"crossref","unstructured":"Huang, H. et al. miR-5100 promotes tumor growth in lung cancer by targeting Rab6. Cancer Lett. 362(1), 15\u201324 (2015).","DOI":"10.1016\/j.canlet.2015.03.004"},{"key":"73783_CR21","unstructured":"Wang, T., Liu, X., Tian, Q., Liang, T. & Chang, P. Increasing expression of miR-5100 in non-small-cell lung cancer and correlation with prognosis. Eur. Rev. Med. Pharmacol. Sci.21 (16), 3592\u20132597 (2017)."},{"key":"73783_CR22","doi-asserted-by":"crossref","unstructured":"Zhang, H. M. et al. MKL1\/miR-5100\/CAAP1 loop regulates autophagy and apoptosis in gastric cancer cells. Neoplasia. 22(5), 220\u2013230 (2020).","DOI":"10.1016\/j.neo.2020.03.001"},{"key":"73783_CR23","doi-asserted-by":"crossref","unstructured":"Chijiiwa, Y. et al. Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL. Int. J. Oncol. 48(4), 1688\u20131700 (2016).","DOI":"10.3892\/ijo.2016.3389"},{"key":"73783_CR24","doi-asserted-by":"crossref","unstructured":"Wei, Z., Lyu, B., Hou, D. & Liu, X. Mir-5100 mediates Proliferation, Migration and Invasion of oral squamous cell carcinoma cells Via Targeting SCAI. J. Invest. Surg. 34(8), 834\u2013841 (2021).","DOI":"10.1080\/08941939.2019.1701754"},{"issue":"9","key":"73783_CR25","doi-asserted-by":"publisher","first-page":"e107986","DOI":"10.1371\/journal.pone.0107986","volume":"9","author":"Y Tan","year":"2014","unstructured":"Tan, Y. et al. A serum MicroRNA panel as potential biomarkers for Hepatocellular Carcinoma related with Hepatitis B Virus. PLoS One. 9(9), e107986 (2014).","journal-title":"PLoS One"},{"issue":"10","key":"73783_CR26","doi-asserted-by":"publisher","first-page":"4606","DOI":"10.18632\/aging.204102","volume":"14","author":"J Shen","year":"2022","unstructured":"Shen, J. et al. Comprehensive analysis of expression profiles and prognosis of TRIM genes in human kidney clear cell carcinoma. Aging. 14(10), 4606\u20134617 (2022).","journal-title":"Aging"},{"key":"73783_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/1571045","volume":"2019","author":"D Qin","year":"2019","unstructured":"Qin, D. et al. A circulating miRNA-Based Scoring System established by WGCNA to predict Colon cancer. Anal. Cell. Pathol.2019, 1\u20137 (2019).","journal-title":"Anal. Cell. Pathol."},{"issue":"1","key":"73783_CR28","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1007\/s10517-016-3358-6","volume":"161","author":"EN Knyazev","year":"2016","unstructured":"Knyazev, E. N. et al. Shkurnikov MYu. MicroRNA hsa-miR-4674 in hemolysis-free blood plasma is Associated with distant metastases of Prostatic Cancer. Bull. Exp. Biol. Med.161(1), 112\u2013115 (2016).","journal-title":"Bull. Exp. Biol. Med."},{"issue":"12","key":"73783_CR29","doi-asserted-by":"publisher","first-page":"101330","DOI":"10.1016\/j.xcrm.2023.101330","volume":"4","author":"H Kameyama","year":"2023","unstructured":"Kameyama, H. et al. Needle biopsy accelerates pro-metastatic changes and systemic dissemination in breast cancer: implications for mortality by surgery delay. Cell. Rep. Med.4(12), 101330 (2023).","journal-title":"Cell. Rep. Med."},{"key":"73783_CR30","doi-asserted-by":"crossref","unstructured":"Klein, E. A. et al. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Ann. Oncol. 32(9), 1167\u20131177 (2021).","DOI":"10.1016\/j.annonc.2021.05.806"},{"key":"73783_CR31","unstructured":"Cohen, J. D. et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 359(6378), 926\u2013930 (2018)."},{"key":"73783_CR32","doi-asserted-by":"crossref","unstructured":"Chen, X. et al. Non-invasive early detection of cancer four years before conventional diagnosis using a blood test. Nat. Commun. 11(1), 3475 (2020).","DOI":"10.1038\/s41467-020-17316-z"},{"key":"73783_CR33","unstructured":"Cristiano, S. et al. Genome-wide cell-free DNA fragmentation in patients with cancer. Nature. 570(7761), 385\u2013389 (2019)."},{"issue":"S_7","key":"73783_CR34","doi-asserted-by":"publisher","first-page":"S575","DOI":"10.1016\/j.annonc.2022.07.106","volume":"33","author":"C Douville","year":"2022","unstructured":"Douville, C. et al. Multi-cancer early detection through evaluation of aneuploidy, methylation, and protein biomarkers in plasma. Ann. Oncol.33(S_7), S575 (2022).","journal-title":"Ann. Oncol."},{"issue":"S_7","key":"73783_CR35","doi-asserted-by":"publisher","first-page":"S961","DOI":"10.1016\/j.annonc.2022.07.1029","volume":"33","author":"D Schrag","year":"2022","unstructured":"Schrag, D. et al. A prospective study of a multi-cancer early detection blood test. Ann. Oncol.33(S_7), S961 (2022).","journal-title":"Ann. Oncol."},{"issue":"7","key":"73783_CR36","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/S1470-2045(23)00277-2","volume":"24","author":"BD Nicholson","year":"2023","unstructured":"Nicholson, B. D. et al. Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): a large-scale, observational cohort study. Lancet Oncol.24(7), 733\u2013743 (2023).","journal-title":"Lancet Oncol."},{"key":"73783_CR37","doi-asserted-by":"crossref","unstructured":"Lehman, C. D. et al. National Performance Benchmarks for Modern Screening Digital Mammography: Update from the breast Cancer Surveillance Consortium. Radiology.283(1), 49\u201358 (2017).","DOI":"10.1148\/radiol.2016161174"},{"key":"73783_CR38","unstructured":"U. S. Food and Drug Administration. Cologuard Summary of Safety and Effectiveness Data (Premarket Approval Application P130017). (2014)."},{"key":"73783_CR39","doi-asserted-by":"crossref","unstructured":"National Lung Screening Trial Research Team et al. Results of initial low-dose computed tomographic screening for lung cancer. N Engl. J. Med. 368(21), 1980\u20131991 (2013).","DOI":"10.1056\/NEJMoa1209120"},{"key":"73783_CR40","doi-asserted-by":"crossref","unstructured":"Ritchie, M. E. et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43(7), e47 (2015).","DOI":"10.1093\/nar\/gkv007"},{"issue":"D1","key":"73783_CR41","doi-asserted-by":"publisher","first-page":"D127","DOI":"10.1093\/nar\/gkz757","volume":"48","author":"Y Chen","year":"2020","unstructured":"Chen, Y. & Wang, X. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res.48(D1), D127\u2013D131 (2020).","journal-title":"Nucleic Acids Res."},{"issue":"5","key":"73783_CR42","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu, G., Wang, L. G., Han, Y. & He, Q. Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 16(5), 284\u2013287 (2012).","journal-title":"OMICS"},{"issue":"3","key":"73783_CR43","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","volume":"2","author":"T Wu","year":"2021","unstructured":"Wu, T. et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innov. (Cambridge (Mass)). 2(3), 100141 (2021).","journal-title":"Innov. (Cambridge (Mass))"},{"issue":"1","key":"73783_CR44","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res.28(1), 27\u201330 (2000).","journal-title":"Nucleic Acids Res."},{"issue":"D1","key":"73783_CR45","doi-asserted-by":"publisher","first-page":"D587","DOI":"10.1093\/nar\/gkac963","volume":"51","author":"M Kanehisa","year":"2023","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Kawashima, M. & Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res.51(D1), D587\u2013D592 (2023).","journal-title":"Nucleic Acids Res."},{"issue":"D1","key":"73783_CR46","doi-asserted-by":"publisher","first-page":"D679","DOI":"10.1093\/nar\/gkad960","volume":"52","author":"A Agrawal","year":"2024","unstructured":"Agrawal, A. et al. WikiPathways 2024: next generation pathway database. Nucleic Acids Res.52(D1), D679\u2013D689 (2024).","journal-title":"Nucleic Acids Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-73783-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-73783-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-73783-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T18:04:13Z","timestamp":1727719453000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-73783-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,27]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["73783"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-73783-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,27]]},"assertion":[{"value":"17 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"J.Z. and H.H. are named inventors on a patent of the diagnostic model developed in this study. HH is a cofounder of, and holds equity in miRoncol Diagnostics, Inc, a company that seeks to commercialize the diagnostic model. All other authors do not hold any competing interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22136"}}