{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:26:55Z","timestamp":1790015215471,"version":"4.0.1"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"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. Oncol."],"abstract":"<jats:p>Liquid biopsy based on circulating cell-free DNA (cfDNA) methylation has become a leading non-invasive strategy for multi-cancer early detection (MCED). Aberrant DNA methylation arises at the early stage of tumorigenesis and displays cancer-type-specific signatures, enabling early capture of tumor-derived epigenetic signals. High-throughput sequencing, digital PCR and machine learning algorithms have greatly improved the sensitivity and specificity of methylation-based assays. Large-scale clinical trials including CCGA, PATHFINDER, THUNDER and GUIDE have validated that MCED tests achieve high specificity (&amp;gt;99%) and reliable accuracy for tissue of origin prediction. Integrating methylomics with fragmentomics further boosts early detection performance, especially for early-stage tumors with low ctDNA shedding. Nevertheless, clinical translation still faces notable hurdles, including technical standardization, biological confounding factors, high cost and the demand for large-scale prospective mortality endpoint validation. Future development will rely on multi-omics integration, optimized bioinformatic pipelines and standardized interventional trials to lower cancer-specific mortality. In summary, methylation liquid biopsy is poised to reshape cancer screening from single-organ late diagnosis to multi-cancer early intervention, offering profound prospects for precision oncology.<\/jats:p>","DOI":"10.3389\/fonc.2026.1850041","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:51:13Z","timestamp":1781671873000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Early detection of multiple cancers: the era of methylation-based liquid biopsy"],"prefix":"10.3389","volume":"16","author":[{"given":"Yajie","family":"Lin","sequence":"first","affiliation":[{"name":"Bioinformatic Center, Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zekai","family":"Hu","sequence":"additional","affiliation":[{"name":"Bioinformatic Center, Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyao","family":"Shuai","sequence":"additional","affiliation":[{"name":"Bioinformatic Center, Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaowei","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University","place":["Huzhou, Zhejiang, China"]},{"name":"Huzhou Key Laboratory of Precision Medicine Research and Translation for Infectious Diseases, Affiliated Central Hospital, Huzhou University","place":["Huzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hainv","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Infection, Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junsheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Bioinformatic Center, Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","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":"B2","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":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01700-2","article-title":"Blood-based tests for multicancer early detection (PATHFINDER): a pros pective cohort study","volume":"402","author":"Schrag","year":"2023","journal-title":"Lancet"},{"key":"B4","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":"B5","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\u2606","volume":"34","author":"Gao","year":"2023","journal-title":"Ann Oncol"},{"key":"B6","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 g astrointestinal cancers using targeted DNA methylation and fragmentomi cs sequencing","volume":"24","author":"Huang","year":"2025","journal-title":"Mol Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.70071","article-title":"The INSPECTOR study: enhanced feasibility for clinical translation of a multi-cancer early detection method based on enzyme-assisted high si gnal-to-noise ratio sequencing of methylated circulating tumor DNA","volume":"45","author":"Luo","year":"2025","journal-title":"Cancer Commun Lond"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.10.038","article-title":"Clinical validation of a multi-model blood cfDNA methylation assay for early-stage gastrointestinal cancer screening","author":"Zhu","year":"2025","journal-title":"J Adv Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1186\/s12885-024-12626-7","article-title":"TOTEM: a multi-cancer detection and localization approach using circulating tumor DNA methylation markers","volume":"24","author":"Xiong","year":"2024","journal-title":"BMC Cancer"},{"key":"B10","doi-asserted-by":"publisher","first-page":"RP89083","DOI":"10.7554\/eLife.89083","article-title":"Multimodal analysis of methylomics and fragmentomics in plasma cell-fr ee DNA for multi-cancer early detection and localization","volume":"12","author":"Nguyen","year":"2023","journal-title":"Elife"},{"key":"B11","doi-asserted-by":"publisher","first-page":"9625","DOI":"10.1038\/s41467-025-64094-7","article-title":"Real-world data and clinical experience from over 100,000 multi-cancer early detection tests","volume":"16","author":"Matrana","year":"2025","journal-title":"Nat Commun"},{"key":"B12","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s12943-023-01866-z","article-title":"Efficacy of cell-free DNA methylation-based blood test for colorectal cancer screening in high-risk population: a prospective cohort study","volume":"22","author":"Zhao","year":"2023","journal-title":"Mol Cancer"},{"key":"B13","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":"B14","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":"B15","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-25-0903","article-title":"Framework to select multi-cancer detection assays in the national cancer institute\u2019s vanguard study","volume":"34","author":"LeeVan","year":"2025","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djag001","article-title":"Performance of multiple multi-cancer detection tests using a large independent reference set (Alliance A212102)","volume":"118","author":"Wood","year":"2026","journal-title":"J Natl Cancer Inst"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01498-4","article-title":"Estimating the population health impact of a multi-cancer early detection genomic blood test to complement existing screening in the US and UK","volume":"125","author":"Hackshaw","year":"2021","journal-title":"Br J Cancer"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1177\/03008916221133136","article-title":"Multi-cancer early detection test sensitivity for cancers with and without current population-level screening options","volume":"109","author":"Shao","year":"2023","journal-title":"Tumori"},{"key":"B19","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":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/jech-2023-220834","article-title":"Impact of screening participation on modelled mortality benefits of a multi-cancer early detection test by socioeconomic group in England","volume":"78","author":"Smittenaar","year":"2024","journal-title":"J Epidemiol Community Health"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s40273-022-01181-3","article-title":"The potential value-based price of a multi-cancer early detection genomic blood test to complement current single cancer screening in the USA","volume":"40","author":"Tafazzoli","year":"2022","journal-title":"Pharmacoeconomics"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adp1704","article-title":"Multiplex digital profiling of DNA methylation heterogeneity for sensitive and cost-effective cancer detection in low-volume liquid biopsies","volume":"10","author":"Zhao","year":"2024","journal-title":"Sci Adv"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvaa100","article-title":"Enhanced performance of DNA methylation markers by simultaneous measurement of sense and antisense DNA strands after cytosine conversion","volume":"66","author":"Jensen","year":"2020","journal-title":"Clin Chem"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2024.06.007","article-title":"Analytical validation of an early detection pancreatic cancer test using 5-hydroxymethylation signatures","volume":"26","author":"Chowdhury","year":"2024","journal-title":"J Mol Diagn"},{"key":"B25","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1186\/s13148-021-01183-6","article-title":"Cell-free DNA 5-hydroxymethylcytosine profiles of long non-coding RNA genes enable early detection and progression monitoring of human cancers","volume":"13","author":"Zhou","year":"2021","journal-title":"Clin Epigenet"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1016\/j.ccell.2022.10.022","article-title":"Evaluation of cell-free DNA approaches for multi-cancer early detection","volume":"40","author":"Jamshidi","year":"2022","journal-title":"Cancer Cell"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101717","article-title":"Early detection and prognosis prediction for colorectal cancer by circulating tumour DNA methylation haplotypes: A multicentre cohort study","volume":"55","author":"Mo","year":"2023","journal-title":"EClinicalMedicine"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/s43556-026-00426-3","article-title":"Development and validation of a high-confidence diagnostic model integrating ctDNA methylation and serum biomarkers for early-stage hepatocellular carcinoma detection","volume":"7","author":"Wu","year":"2026","journal-title":"Mol BioMed"},{"key":"B29","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.molmed.2020.12.011","article-title":"Liquid biopsy of methylation biomarkers in cell-free DNA","volume":"27","author":"Luo","year":"2021","journal-title":"Trends Mol Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abn4030","article-title":"Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients","volume":"8","author":"Cheruba","year":"2022","journal-title":"Sci Adv"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/mc.70101","article-title":"Whole-genome bisulfite sequencing identifies blood-based DNA methylation biomarker for hepatocellular carcinoma","volume":"65","author":"Zhao","year":"2026","journal-title":"Mol Carcinog"},{"key":"B32","doi-asserted-by":"publisher","first-page":"mjad023","DOI":"10.1093\/jmcb\/mjad023","article-title":"Accurate prediction of pan-cancer types using machine learning with minimal number of DNA methylation sites","volume":"15","author":"Ning","year":"2023","journal-title":"J Mol Cell Biol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-021-00746-5","article-title":"Ultrasensitive detection of circulating tumour DNA via deep methylation sequencing aided by machine learning","volume":"5","author":"Liang","year":"2021","journal-title":"Nat BioMed Eng"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2025.101076","article-title":"Exploration of multi-omics liquid biopsy approaches for multi-cancer early detection: The PROMISE study","volume":"7","author":"Duan","year":"2026","journal-title":"Innovation Camb"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2209852119","article-title":"Epigenetic analysis of cell-free DNA by fragmentomic profiling","volume":"119","author":"Zhou","year":"2022","journal-title":"Proc Natl Acad Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvae118","article-title":"Methylation-associated nucleosomal patterns of cell-free DNA in cancer patients and pregnant women","volume":"70","author":"Zhu","year":"2024","journal-title":"Clin Chem"},{"key":"B37","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s13073-026-01603-3","article-title":"A computational framework for sensitive tumor detection and accurate subtyping using shallow cell-free DNA methylome sequencing","volume":"18","author":"Paoli","year":"2026","journal-title":"Genome Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"40892","DOI":"10.1038\/s41598-025-24708-y","article-title":"RECAP-seq: restriction enzyme-based CpG-methylated fragment amplification for early cancer detection","volume":"15","author":"Shin","year":"2025","journal-title":"Sci Rep"},{"key":"B39","doi-asserted-by":"publisher","first-page":"33004","DOI":"10.1038\/s41598-025-18278-2","article-title":"Improved circulating tumor DNA identification for detection of esophageal squamous cell carcinoma by enzymatic methyl sequencing and hybrid neural network","volume":"15","author":"Shen","year":"2025","journal-title":"Sci Rep"},{"key":"B40","doi-asserted-by":"publisher","first-page":"6113","DOI":"10.1038\/s41467-024-50471-1","article-title":"Tumor detection by analysis of both symmetric- and hemi-methylation of plasma cell-free DNA","volume":"15","author":"Hua","year":"2024","journal-title":"Nat Commun"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15052","article-title":"Prediction model for Malignant pulmonary nodules based on cfMeDIP\u2010seq and machine learning","volume":"112","author":"Qi","year":"2021","journal-title":"Cancer Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.crmeth.2022.100294","article-title":"Sensitive and reproducible cell-free methylome quantification with synthetic spike-in controls","volume":"2","author":"Wilson","year":"2022","journal-title":"Cell Rep Methods"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0932-2","article-title":"Detection and discrimination of intracranial tumors using plasma cell-free DNA methylomes","volume":"26","author":"Nassiri","year":"2020","journal-title":"Nat Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-026-01116-3","article-title":"A pan-cancer compendium of 1,294 plasma cell-free DNA methylomes and fragmentomes enabling multicancer detection","volume":"7","author":"Zeng","year":"2026","journal-title":"Nat Cancer"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2023.08.010","article-title":"Circulating cell-free DNA-based multi-cancer early detection","volume":"10","author":"Zhang","year":"2024","journal-title":"Trends Cancer"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70594","article-title":"Liquid biopsy biomarkers for early detection of gastrointestinal cancers: Current landscape and emerging technologies","volume":"16","author":"Anees","year":"2026","journal-title":"Clin Transl Med"},{"key":"B47","doi-asserted-by":"publisher","first-page":"158","DOI":"10.3390\/biomedicines14010158","article-title":"Liquid biopsy in early screening of cancers: emerging technologies and new prospects","volume":"14","author":"Zhu","year":"2026","journal-title":"Biomedicines"},{"key":"B48","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s13045-022-01351-y","article-title":"Liquid biopsy: current technology and clinical applications","volume":"15","author":"Nikanjam","year":"2022","journal-title":"J Hematol Oncol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"767","DOI":"10.3390\/cancers18050767","article-title":"Urine-based cfDNA ensemble modeling for early detection of bladder cancer using whole-genome methylation sequencing","volume":"18","author":"Kim","year":"2026","journal-title":"Cancers Bsl"},{"key":"B50","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1038\/s43856-025-01235-5","article-title":"Nanopore based RNA methylation profiling of a circulating lung cancer biomarker","volume":"5","author":"Sanchez-Delgado","year":"2025","journal-title":"Commun Med Lond"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2025.152636","article-title":"Clinical translation of ctDNA epigenetic signatures in lung cancer: An integrated strategy for early detection, therapeutic guidance, and prognostic stratification","volume":"783","author":"You","year":"2025","journal-title":"Biochem Biophys Res Commun"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1200\/PO.24.00269","article-title":"A targeted methylation-based multicancer early detection blood test pr eferentially detects high-grade prostate cancer while minimizing overd iagnosis of indolent disease","volume":"8","author":"Mahal","year":"2024","journal-title":"JCO Precis Oncol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.3390\/cancers16112001","article-title":"Current challenges of methylation-based liquid biopsies in cancer diag nostics","volume":"16","author":"Rendek","year":"2024","journal-title":"Cancers Bsl"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdac034","article-title":"Tapping into the genome: the role of CSF ctDNA liquid biopsy in glioma","volume":"4","author":"Friedman","year":"2022","journal-title":"Neuro-Oncol Adv"},{"key":"B55","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.humpath.2012.06.009","article-title":"Microvessel density is not increased in prostate cancer: digital imaging of routine sections and tissue microarrays","volume":"44","author":"Tretiakova","year":"2013","journal-title":"Hum Pathol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/labinvest.2011.153","article-title":"Microvascular density as an independent predictor of clinical outcome in renal cell carcinoma: an automated image analysis study","volume":"92","author":"Iakovlev","year":"2012","journal-title":"Lab Invest"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy552","article-title":"Clonal haematopoiesis: a source of biological noise in cell-free DNA analyses","volume":"30","author":"Abbosh","year":"2019","journal-title":"Ann Oncol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01525","article-title":"The role of epigenetics in autoimmune\/inflammatory disease","volume":"10","author":"Surace","year":"2019","journal-title":"Front Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.030841","article-title":"Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer","volume":"53","author":"Wynter","year":"2004","journal-title":"Gut"},{"key":"B60","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1186\/s13059-024-03381-w","article-title":"A comprehensive map of the aging blood methylome in humans","volume":"25","author":"Seale","year":"2024","journal-title":"Genome Biol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s13058-022-01554-8","article-title":"Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies","volume":"24","author":"Dugu\u00e9","year":"2022","journal-title":"Breast Cancer Res"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1016\/j.ccell.2023.07.013","article-title":"Integrative multi-omic cancer profiling reveals DNA methylation patterns associated with therapeutic vulnerability and cell-of-origin","volume":"41","author":"Liang","year":"2023","journal-title":"Cancer Cell"},{"key":"B63","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1186\/s12916-022-02681-x","article-title":"Potential clinical utility of liquid biopsy in early-stage non-small c ell lung cancer","volume":"20","author":"Shen","year":"2022","journal-title":"BMC Med"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3343\/alm.2022.42.2.141","article-title":"Clinical practice guidelines for pre-analytical procedures of plasma epidermal growth factor receptor variant testing","volume":"42","author":"Shin","year":"2022","journal-title":"Ann Lab Med"},{"key":"B65","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.ajpath.2018.03.020","article-title":"Circulating tumor cells and cell-free DNA in pancreatic ductal adenoca rcinoma","volume":"189","author":"Gall","year":"2019","journal-title":"Am J Pathol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.euros.2021.12.006","article-title":"Circulating tumor DNA in patients with renal cell carcinoma. A systema tic review of the literature","volume":"37","author":"Geertsen","year":"2022","journal-title":"Eur Urol Open Sci"},{"key":"B67","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13072-025-00616-3","article-title":"Comparison of current methods for genome-wide DNA methylation profiling","volume":"18","author":"de Abreu","year":"2025","journal-title":"Epigenet Chromatin"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-026-01674-7","article-title":"Enhanced multicancer screening assay through whole-genome methylation sequencing-based multimodal cell-free DNA analysis","volume":"58","author":"Jeong","year":"2026","journal-title":"Exp Mol Med"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01119-5","article-title":"Cancer signature ensemble integrating cfDNA methylation, copy number, and fragmentation facilitates multi-cancer early detection","volume":"55","author":"Kim","year":"2023","journal-title":"Exp Mol Med"},{"key":"B70","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s13148-025-01959-0","article-title":"Comprehensive comparison of enzymatic and bisulfite DNA methylation analysis in clinically relevant samples","volume":"17","author":"Nuttall","year":"2025","journal-title":"Clin Epigenet"},{"key":"B71","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s13148-025-01855-7","article-title":"Comparative performance evaluation of bisulfite- and enzyme-based DNA conversion methods","volume":"17","author":"Simons","year":"2025","journal-title":"Clin Epigenet"},{"key":"B72","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s13148-025-01901-4","article-title":"Comparison of enzymatic and bisulfite conversion of circulating cell-free tumor DNA for DNA methylation analyses","volume":"17","author":"Kresse","year":"2025","journal-title":"Clin Epigenet"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1080\/20565623.2024.2395244","article-title":"A consultation and work-up diagnosis protocol for a multicancer early detection test: a case series study","volume":"10","author":"Dang Nguyen","year":"2024","journal-title":"Future Sci OA"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-25-0283","article-title":"Molecular cancer signal localization in MCED testing minimizes radiation and imaging burden compared to whole body imaging approaches","volume":"19","author":"Massart","year":"2026","journal-title":"Cancer Prev Res Phila"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-24-0468","article-title":"Clinical evaluation of cancer signal origin prediction and diagnostic resolution following multicancer early detection testing in the PATHFINDER study","volume":"18","author":"Marinac","year":"2025","journal-title":"Cancer Prev Res Phila"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1017\/S0963180124000744","article-title":"Ethical considerations and implications of multi-cancer early detectio n screening: Reliability, access and cost to test and treat","volume":"34","author":"Sempere","year":"2025","journal-title":"Cambridge Q Healthcare Ethics"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-04111-w","article-title":"The ethics of multi-cancer screening","volume":"32","author":"Callender","year":"2026","journal-title":"Nat Med"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1850041\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:51:24Z","timestamp":1781671884000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1850041\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":77,"alternative-id":["10.3389\/fonc.2026.1850041"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1850041","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]},"article-number":"1850041"}}