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Background: CRC remains a leading cause of cancer mortality, while early detection enables more effective therapy; methylated ctDNA testing is a promising non-invasive approach for detection and monitoring. Methods: searches of Web of Science, PubMed, and Scopus up to Dec 30, 2023.",{"@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/advances-in-blood-dna-methylation-based-assay-for-colorectal-cancer-early-detection-a-systematic-updated-review/333795/",{"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/advances-in-blood-dna-methylation-based-assay-for-colorectal-cancer-early-detection-a-systematic-updated-review/333795.png","ImageObject",300,407,{"name":92,"@type":93},"Levi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main purpose of the systematic review?","Question",{"text":112,"@type":113},"The review summarizes methylated ctDNA markers reported in the past decade for early CRC detection and identifies key technical challenges hindering clinical implementation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which databases and time range were searched?",{"text":117,"@type":113},"The study searched Web of Science, PubMed, and Scopus up to December 30, 2023, focusing on articles published after 2012.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the key findings about biomarker performance?",{"text":121,"@type":113},"Single biomarkers such as MYO1-G, SEPT9, SDC2, and JAM3 showed the highest sensitivity for polyps and stage I/II CRC, while multi-biomarker combinations were identified for similar settings.","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},333795,1790124204,{"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":34,"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":36,"preview_page_count":4},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Gastroenterology and Hepatology From Bed to Bench.  \n2024 RIGLD, Research Institute for Gastroenterology and Liver Diseases  \nSYSTEMATIC REVIEW  \np-ISSN: 2008-2258 e-ISSN: 2008-4234  \nAdvances in blood DNA methylation-based assay for colorectal cancer early detection: a systematic updated review  \nMilad Khabbazpour1, Masoud Tat1, Ashraf Karbasi2, Mohammad Ali Abyazi2, Ghazal Khodadoustan3, Zohreh Heidary4, Majid Zaki-Dizaji1  \n1Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran  \n2Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran  \n3Department of Cell and Molecular Biology and Microbiology, Faculty of biological science and technology, University of Isfahan, Isfahan, Iran  \n4 Vali-e-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran  \nABSTRACT  \nAim: A systematic review was conducted to summarize the methylated circulating tumor DNA (ctDNA) markers reported over the last decade for early detection of colorectal cancer (CRC) and to identify the main technical challenges that are impeding their clinical implementation.  \nBackground: CRC is a major cause of cancer deaths worldwide, but early detection is key for successful treatment. Non-invasive methods such as methylated ctDNA testing show promise for improving detection and monitoring ofCRC.  \nMethods: A comprehensive search was performed using Web of Science, PubMed, and Scopus up to December 30, 2023, limited to articles published in the last 10 years (after 2012), while including advanced adenoma/stage 0 or stage I/II samples in biomarker validation.  \nResults: After identifying 694 articles, removing duplicates and screening titles, abstracts, and full texts, a total of 62 articles were found to meet the inclusion criteria. Among the single biomarkers, MYO1-G, SEPT9, SDC2, and JAM3 revealed the highest sensitivity for polyps and stage I/II CRC. For multi-biomarkers with suitable sensitivity, combinations of SFRP1, SFRP2, SDC2, PRIMA1, or ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, VIM or ZFHX4, ZNF334, ELOVL2, UNC5C, LOC146880, SFMBT2, GFRA1 were identified for polyps and stage I/II CRC.  \nConclusion: Enhancing sensitivity and specificity of molecular screening methods is crucial for improving CRC detection. Identifying a select few valuable biomarkers is key to reducing costs, despite challenges posed by low ctDNA levels in plasma , particularly in early-stage cancers.  \nKeywords: Colorectal cancer, Circulating tumor DNA, DNA methylation, Liquid biopsy, Cancer biomarker, Early detection  \n(Please cite as: Khabbazpour M, Tat M, Karbasi A, Abyazi MA, Khodadoustan G, Heidary Z, Zaki-Dizaji M. Advances in blood DNA methylation-based assay for colorectal cancer early detection: a systematic updated review. Gastroenterol Hepatol Bed Bench 2024;17(3):225-240. [https://doi.org/10.22037/ghfbb.v17i3.2978](https://doi.org/10.22037/ghfbb.v17i3.2978)).  \nIntroduction  \nDespite advances in detection and treatment methods, colorectal cancer (CRC) is the second most deadly cancer and the third most common malignant tumor among men and women worldwide (1, 2). CRC survival rates are closely linked to early detection,  \nReceived: 02 April 2024 Accepted: 04 June 2024  \nReprint or Correspondence: Majid Zaki-Dizaji, PhD, Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. [E-mail:](E-mail: majid.zakidizaji@gmail.com)[ majid.zakidizaji@gmail.com](E-mail: majid.zakidizaji@gmail.com)  \n[ORCID ID:](ORCID ID: 0000-0003-1642-3289)[ 0000-0003-1642-3289](ORCID ID: 0000-0003-1642-3289)  \nwhich ranges from a 90% five-year survival rate in stage I disease to 10% five-year survival in stage IV disease (3). Approximately 60% of CRC patients at diagnosis present with either locally advanced lesions or distant metastases. This advanced stage unfortun","cbCaibx3yKHSF6rA","https://ap.wps.com/l/cbCaibx3yKHSF6rA","pdf",963758,16,"English","# Abstract\n## Aim\n## Background\n## Methods\n## Results\n## Conclusion\n# Introduction","[{\"question\":\"What is the main purpose of the systematic review?\",\"answer\":\"The review summarizes methylated ctDNA markers reported in the past decade for early CRC detection and identifies key technical challenges hindering clinical implementation.\"},{\"question\":\"Which databases and time range were searched?\",\"answer\":\"The study searched Web of Science, PubMed, and Scopus up to December 30, 2023, focusing on articles published after 2012.\"},{\"question\":\"What were the key findings about biomarker performance?\",\"answer\":\"Single biomarkers such as MYO1-G, SEPT9, SDC2, and JAM3 showed the highest sensitivity for polyps and stage I/II CRC, while multi-biomarker combinations were identified for similar settings.\"}]","Advances in blood DNA methylation-based assay for colorectal cancer early detection - a systematic updated review | PDF",1790004133]