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The study addresses the limited ability of current diagnostics to detect disease at advanced stages and the scarcity of comprehensive cfDNA epigenetic landscape investigations. GastroAlert integrates cfDNA methylation, nucleosome footprinting, and fragmentation features, using targeted enzymatic methylation sequencing and rigorous validation across discovery and independent external datasets to assess diagnostic accuracy, including early-stage performance.",{"@graph":69,"@context":122},[70,84,105],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/gastroalert-a-multimodal-epigenetic-blood-test-for-early-detection-of-gastric-cancer-using-cell-free-dna/349603/",{"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/gastroalert-a-multimodal-epigenetic-blood-test-for-early-detection-of-gastric-cancer-using-cell-free-dna/349603.png","ImageObject",300,407,{"name":92,"@type":93},"anakgang17","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is GastroAlert and what does it detect?","Question",{"text":112,"@type":113},"GastroAlert is a multimodal epigenetic blood test that detects gastric cancer using features derived from cell-free DNA.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which biological features are integrated into the GastroAlert test?",{"text":117,"@type":113},"It combines cfDNA methylation, nucleosome footprinting, and DNA fragmentation characteristics in a single diagnostic approach.",{"name":119,"@type":110,"acceptedAnswer":120},"How was GastroAlert validated and what performance was reported?",{"text":121,"@type":113},"Performance was assessed using cross-validation in a discovery dataset and rigorously validated in an independent external dataset, reporting high AUC values including strong results for early-stage cases.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},349603,1790153208,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962090883568,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Xu et al. Mil Med Res 2026  \n[https://doi.org/10.1016/j.mmr.2026.100066](https://doi.org/10.1016/j.mmr.2026.100066)  \nRESEARCH Open Access  \nGastroAlert: a multimodal epigenetic blood test for early detection of gastric cancer using cell-free DNA  \nYong-Jie Xu1†, Jian-Feng Xu2†, Chang-Fa Xia1†, Yu-Jie Wu1†, Dian-Ge Li2, Tie-Yan Liu2, Huai-Ping Cui3, Jin Zhang4, Liang Shang3* and Wan-Qing Chen5*  \nAbstract  \nBackground: Gastric cancer remains a leading cause of cancer-related mortality worldwide, frequently diagnosed at advanced stages due to the limitations of current diagnostic approaches. While cell-free DNA (cfDNA)-based epigenetic profiling has emerged as a promising avenue for early cancer detection, comprehensive investigations into the epigenetic landscape of cfDNA in gastric cancer remain scarce. To address this gap, we aimed to develop and validate a multimodal epigenetic blood test for the non-invasive detection of gastric cancer.  \nMethods: We developed GastroAlert, a multimodal epigenetic blood test that integrates cfDNA methylation, nucleosome footprinting, and fragmentation features into a single diagnostic approach for gastric cancer detection. A custom-designed capture probe panel was utilized to target gastric cancer-associated differentially methylated CpG sites and functionally relevant genes. Targeted enzymatic methylation sequencing was then performed on a discovery dataset consisting of 136 participants, including 53 gastric cancer patients, 55 individuals with benign gastric conditions, and 28 healthy controls. Subsequently, the diagnostic performance of GastroAlert was rigorously validated in an independent external dataset of 149 participants, comprising 79 gastric cancer cases and 70 non-cancer controls. Results: In cross-validation of the discovery dataset, GastroAlert achieved an area under the receiver operating characteristic curve (AUC) of 0.950 [95% confidence interval (CI) 0.874-0.995], with observed AUCs for conventional protein biomarkers ranging from 0.507 to 0.687. Notably, the locked GastroAlert model exhibited robust and reproducible performance in the independent validation dataset, yielding an AUC of 0.965 (95% CI 0.940-0.989) for distinguishing gastric cancer patients from non-cancer controls. For the clinically critical subset of early-stage gastric cancer cases, the model still maintained high diagnostic efficacy with an AUC of 0.921 (95% CI 0.862-0.980) in the discovery dataset and 0.948 (95% CI 0.910-0.985) in the validation dataset. Among all 79 gastric cancer cases in the validation dataset, the model attained an overall sensitivity of 0.898 (95% CI 0.813-0.948) at a specificity of 0.900 in the validation dataset.  \nConclusions: The findings demonstrate that multimodal epigenetic analysis of cfDNA provides a robust, non-invasive strategy for early gastric cancer detection, with potential clinical utility to improve patient outcomes.  \nKey words Gastric cancer, Early detection, Cell-free DNA, Epigenetic biomarkers  \nBackground  \nGastric cancer remains one of the leading causes of cancerrelated mortality worldwide, with a poor prognosis largely due to late-stage diagnosis [ 1]. Early detection of gastric cancer is crucial for improving survival rates; however, current diagnostic methods, such as endoscopy and biopsy, are invasive and costly, suffering from poor compliance. This limits their effectiveness  \n†Yong-Jie Xu, Jian-Feng Xu, Chang-Fa Xia, and Yu-Jie Wu contributed equally to this work  \n*Correspondence: Liang Shang, [docshang@126.com](docshang@126.com); Wan-Qing Chen, chenwq@ [cicams.ac.cn](cicams.ac.cn)  \n3Department of Gastroenterological Surgery, Shandong Provincial Hospital of Shandong First Medical University, Jinan 250021, China  \n5Office of Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China  \nFull list of author information i","cbCaiatZeQCYxf4W","https://ap.wps.com/l/cbCaiatZeQCYxf4W","pdf",3769511,17,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Background\n## Rationale for non-invasive biomarkers\n## Role of cfDNA and epigenetics","[{\"question\":\"What is GastroAlert and what does it detect?\",\"answer\":\"GastroAlert is a multimodal epigenetic blood test that detects gastric cancer using features derived from cell-free DNA.\"},{\"question\":\"Which biological features are integrated into the GastroAlert test?\",\"answer\":\"It combines cfDNA methylation, nucleosome footprinting, and DNA fragmentation characteristics in a single diagnostic approach.\"},{\"question\":\"How was GastroAlert validated and what performance was reported?\",\"answer\":\"Performance was assessed using cross-validation in a discovery dataset and rigorously validated in an independent external dataset, reporting high AUC values including strong results for early-stage cases.\"}]","GastroAlert - A multimodal epigenetic blood test for early detection of gastric cancer using cell-free DNA | PDF",1790084471,43]