Document Type : Review
Authors
Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran AND Department of Clinical Biochemistry, Kashan University of Medical Sciences, Kashan, Iran
Abstract
Colorectal cancer (CRC) remains a significant global health challenge, largely due to its high mortality when diagnosed at advanced stages. Conventional diagnostic approaches, including colonoscopy and fecal-based assays, are limited by variable sensitivity and suboptimal patient adherence, highlighting the pressing need for non-invasive, robust biomarkers for early detection, prognostic assessment, and therapeutic monitoring. Epigenetic modifications, particularly DNA methylation alterations, have emerged as promising candidates in this regard. This review examines the role of DNA methylation in CRC pathogenesis, emphasizing hypermethylation of tumor suppressor genes and global hypomethylation as central mechanisms driving tumor initiation and progression. We discuss extensively validated methylation biomarkers -including SEPT9, SDC2, MGMT, NDRG4, BMP3, VIM, SFRP, p16, LINE-1, BCAT1, IKZF1, and RASSF1A-and their clinical relevance in CRC screening, prognostication, and recurrence monitoring. Additionally, we address the predictive significance of MLH1 methylation in modulating response to 5-fluorouracil–based chemotherapy, highlighting its potential in guiding personalized treatment strategies. Collectively, these insights underscore the transformative potential of DNA methylation biomarkers in CRC management, facilitating earlier detection, individualized prognostic evaluation, and optimized therapeutic outcomes.
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