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This study analyzed 197 whole-genome bisulfite sequencing datasets across 11 malignancies to identify pan-cancer differentially methylated regions (DMRs). Pan-cancer DMRs showed conserved methylation changes and stronger differential signals in both tissue and cell-free DNA (cfDNA). A diagnostic model using these DMRs detected seven cancer types in plasma cfDNA (n=1,108), reaching 77% sensitivity and 96.9% specificity, including stage I/II sensitivities of 69.6% and 70.4%.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/pan-cancer-differentially-methylated-regions-are-promising-biomarkers-for-non-invasive-diagnosis-in-multiple-cancers/352808/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/pan-cancer-differentially-methylated-regions-are-promising-biomarkers-for-non-invasive-diagnosis-in-multiple-cancers/352808.png","ImageObject",300,407,{"name":92,"@type":93},"Sarah ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What problem does the study address in cancer diagnosis?","Question",{"text":113,"@type":114},"Most DNA methylation biomarkers are specific to one cancer type, which limits their use for detecting multiple cancers efficiently.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were pan-cancer differentially methylated regions (DMRs) identified?",{"text":118,"@type":114},"The researchers analyzed 197 whole-genome bisulfite sequencing datasets spanning 11 malignancies to discover pan-cancer DMRs.",{"name":120,"@type":111,"acceptedAnswer":121},"What diagnostic performance was achieved using pan-cancer DMRs?",{"text":122,"@type":114},"In plasma cfDNA (n=1,108), the model detected seven cancer types with 77% sensitivity and 96.9% specificity, with stage I and II sensitivities of 69.6% and 70.4%, respectively.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},352808,1790463578,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":36},962085320529,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","iScience Article  \nPan-cancer differentially methylated regions are promising biomarkers for non-invasive diagnosis in multiple cancers  \nAuthors  \nZhixian Zhu (朱志贤), Yuanhui Sun (孙元辉), Xionghui Zhou (周雄辉), Guoliang Li (李国亮)  \nCorrespondence  \n[guoliang.li@mail.hzau.edu.cn](guoliang.li@mail.hzau.edu.cn)  \nIn brief  \nDiagnostics; Cancer; Genomics  \n• Pan-cancer DMRs show more significant methylation changes than non-pan-cancer DMRs  \n• High-performance diagnostic models accurately detect cancers using these pan-cancer DMRs  \nZhu et al., 2026, iScience 29, 115425  \nMay 15, 2026 © 2026 Published by Elsevier Inc.  \n[https://doi.org/10.1016/j.isci.2026.115425](https://doi.org/10.1016/j.isci.2026.115425)  \nll  \niScience  \nll  \nOPEN ACCESS  \nArticle  \nPan-cancer differentially methylated regions are promising biomarkers for non-invasive diagnosis in multiple cancers  \nZhixian Zhu (朱志贤),1,2,3 Yuanhui Sun (孙元辉),1,2,3 Xionghui Zhou (周雄辉),1,2 and Guoliang Li (李国亮)1,2,4,*  \n1National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China  \n2Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data, Key Laboratory of Smart Farming Technology for Agricultural Animals, 3D Genomics Research Center, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China  \n3These authors contributed equally  \n4Lead contact  \n*Correspondence: [guoliang.li@mail.hzau.edu.cn](guoliang.li@mail.hzau.edu.cn)  \n[https://doi.org/10.1016/j.isci.2026.115425](https://doi.org/10.1016/j.isci.2026.115425)  \nSUMMARY  \nDNA methylation is a well-established biomarker for cancer diagnosis, and most studies have focused on cancer-type-specific markers. However, methylation biomarkers applicable to multiple cancer types remain largely unexplored, posing a challenge for multi-cancer detection. Here, we identified pan-cancer differentially methylated regions (DMRs) by analyzing 197 whole-genome bisulfite sequencing datasets spanning 11 malignancies. Compared to cancer-type-specific DMRs, pan-cancer DMRs exhibited conserved methylation alterations across tumor types and significantly greater differential methylation in both tissue and cellfree DNA (cfDNA) . A diagnostic model leveraging pan-cancer DMRs accurately detected seven cancer types in a plasma cfDNA dataset (n = 1,108), achieving 77% sensitivity and 96.9% specificity in the test set, with sensitivities of 69.6% and 70.4% for stage I and II patients, respectively. Overall, our findings establish pan-cancer DMRs as promising biomarkers for non-invasive diagnosis of multiple cancer types.  \nINTRODUCTION  \nCancer remains the second leading cause of death worldwide, accounting for nearly 10 million deaths in 2022.1 Early diagnosis is critical for improving treatment outcomes. Patients diagnosed at early stages have significantly better survival prospects, with average 5-year survival rate of 91%, through surgical or pharmacological interventions.2 In contrast, average 5-year survival rate of those diagnosed at advanced stages is only 26% .2 ,3 Therefore, early detection of cancer is a crucial public health strategy to improve patient outcomes.4  \nDNA methylation plays a pivotal role in the initiation and progression of cancer.5 Aberrant DNA methylation patterns are early and widespread events in tumorigenesis.6 Compared to genomic alterations, DNA methylation changes exhibit lower heterogeneity and higher stability, positioning it as one of the most promising biomarkers for cancer detection.7 ,8 Cell-free DNA (cfDNA), which carries the methylation patterns of its originating cells, has emerged as a key tool for developing non-invasive diagnostic approaches.9  \nWhile many DNA methylation biomarkers have been identified for specific cancer types, including lung,10 colorectal,11 and liver12 cancers, these biomarkers are generally limited to individual cancer types and c","cbCaieGOvZkKvP0n","https://ap.wps.com/l/cbCaieGOvZkKvP0n","pdf",5385900,16,"English","# Summary\n# Introduction\n## Cancer burden and the need for early detection\n## DNA methylation as a biomarker\n## Limits of current cancer-type-specific markers\n## Rationale for pan-cancer methylation biomarkers\n# Methods overview\n## Identification using WGBS datasets across 11 cancers\n# Findings overview\n## Conserved methylation alterations across tumor types\n## Diagnostic model performance in plasma cfDNA","[{\"question\":\"What problem does the study address in cancer diagnosis?\",\"answer\":\"Most DNA methylation biomarkers are specific to one cancer type, which limits their use for detecting multiple cancers efficiently.\"},{\"question\":\"How were pan-cancer differentially methylated regions (DMRs) identified?\",\"answer\":\"The researchers analyzed 197 whole-genome bisulfite sequencing datasets spanning 11 malignancies to discover pan-cancer DMRs.\"},{\"question\":\"What diagnostic performance was achieved using pan-cancer DMRs?\",\"answer\":\"In plasma cfDNA (n=1,108), the model detected seven cancer types with 77% sensitivity and 96.9% specificity, with stage I and II sensitivities of 69.6% and 70.4%, respectively.\"}]","Pan-cancer differentially methylated regions are promising biomarkers for non-invasive diagnosis in multiple cancers | PDF",1790101474]