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Existing screening approaches have limitations, driving interest in genetic alterations (mutations in oncogenes and tumor suppressor genes) and epigenetic changes such as aberrant DNA methylation and dysregulated microRNA expression. This review highlights molecular biomarkers with improved specificity and sensitivity, including liquid biopsy components—extracellular vesicles, circulating tumor cells, circulating tumor DNA, and circulating tumor RNA—plus methods to analyze them. It also summarizes non-invasive diagnostic kits (Epi proColon, ColoSure, Cologuard) and discusses clinical challenges.",{"@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/non-invasive-colorectal-cancer-screening-methods-focusing-on-diagnostic-genetic-and-epigenetic-markers/457622/",{"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/non-invasive-colorectal-cancer-screening-methods-focusing-on-diagnostic-genetic-and-epigenetic-markers/457622.png","ImageObject",300,407,{"name":92,"@type":93},"Danger Angel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-08","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is early detection important for colorectal cancer?","Question",{"text":112,"@type":113},"Early detection is crucial because it helps prevent CRC deaths. CRC progresses gradually from pre-cancerous lesions, so screening can intercept disease before invasive cancer develops.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which genetic and epigenetic markers are emphasized in CRC screening?",{"text":117,"@type":113},"The review focuses on genetic changes such as mutations in oncogenes and tumor suppressor genes, and epigenetic modifications including aberrant methylation and altered microRNA expression.",{"name":119,"@type":110,"acceptedAnswer":120},"What does liquid biopsy include for colorectal cancer biomarker detection?",{"text":121,"@type":113},"Liquid biopsy components discussed include extracellular vesicles, circulating tumor cells, circulating tumor DNA, and circulating tumor RNA, which can be analyzed to identify molecular biomarkers.","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},457622,1791050468,{"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":39,"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},962090769052,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Behrouzian Fard etal. Cancer Cell International (2026) 26:3 Cancer Cell International  \n[https://doi.org/10.1186/s12935-025-04097-y](https://doi.org/10.1186/s12935-025-04097-y)  \nREVIEW Open Access  \nNon-invasive colorectal cancer screening methods: focusing on diagnostic genetic and epigenetic markers  \nGhazaleh Behrouzian Fard 1, Razieh Amirfakhrian2, Mahdi Hosseini Bafghi 1* and Mehran Gholamin 1*  \nAbstract  \nColorectal cancer (CRC) is the third most prevalent cancer and one of the leading causes of cancer-related mortality in the world. Early detection is crucial in preventing deaths, but current screening methods have various limitations. So today, much attention is focused on genetic changes, including mutations in oncogenes and tumor suppressor genes, and epigenetic modifications such as aberrant methylation and alterations in the expression of specific microRNAs that contribute to CRC development. This has led to the discovery of more specific and sensitive molecular biomarkers. Furthermore, the use of liquid biopsy, which has a high potential for identifying molecular tumor markers, provides a perspective for overcoming the limitations of conventional screening methods. In this review, we first discuss the intricate molecular processes involved in the development of colorectal tumors. We then delve into the concept of liquid biopsy, exploring its traceable components such as extracellular vesicles, circulating tumor cells, circulating tumor DNAs, and circulating tumor RNAs. We also examine various methods for analyzing these components to identify molecular biomarkers for CRC screening. Additionally, we refer to the development of new diagnostic kits for CRC, such as Epi proColon, ColoSure, and Cologuard, which offer non-invasive utilization of genetic and epigenetic biomarkers. Lastly, we address the current challenges faced in using these biomarkers in a clinical setting. Despite the obstacles, these non-invasive and reliable markers have the potential to enable early detection of CRC and likely increase screening uptake, potentially replacing current modalities.  \nKeywords Colorectal cancer, Non-invasive screening, Liquid biopsy, DNA methylation, MicroRNAs  \n*Correspondence:  \nMahdi Hosseini Bafghi [M_hosseini79@yahoo.com](M_hosseini79@yahoo.com)[ ](M_hosseini79@yahoo.com)Mehran Gholamin [GholaminM@mums.ac.ir](GholaminM@mums.ac.ir)  \n1Department of Laboratory Sciences, Faculty of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran  \n2Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran  \nIntroduction  \nColorectal cancer (CRC) holds the title of the third most prevalent cancer globally and is responsible for the second highest number of cancer-related deaths [1]. It is highly probable that the occurrence and fatality rates of this disease will continue to rise in the coming years [1]. Notably, there has been a considerable surge in the number of cases detected among the elderly demographic [2]. Most cases of CRC occur sporadically in individuals without a family history of this malignancy or inherited genetic mutations that increase the risk of CRC (Fig. 1) [3, 4]. These cases arise through acquired somatic  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the mat","cbCaim6rDtVXrioR","https://ap.wps.com/l/cbCaim6rDtVXrioR","pdf",2098647,18,"English","# Abstract\n# Introduction","[{\"question\":\"Why is early detection important for colorectal cancer?\",\"answer\":\"Early detection is crucial because it helps prevent CRC deaths. CRC progresses gradually from pre-cancerous lesions, so screening can intercept disease before invasive cancer develops.\"},{\"question\":\"Which genetic and epigenetic markers are emphasized in CRC screening?\",\"answer\":\"The review focuses on genetic changes such as mutations in oncogenes and tumor suppressor genes, and epigenetic modifications including aberrant methylation and altered microRNA expression.\"},{\"question\":\"What does liquid biopsy include for colorectal cancer biomarker detection?\",\"answer\":\"Liquid biopsy components discussed include extracellular vesicles, circulating tumor cells, circulating tumor DNA, and circulating tumor RNA, which can be analyzed to identify molecular biomarkers.\"}]","Non-invasive colorectal cancer screening methods - focusing on diagnostic genetic and epigenetic markers | PDF",1790749955,45]