The Role of Epigenetic Biomarkers as Diagnostic, Predictive and Prognostic Factors in Colorectal Cancer.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite significant advances in screening and treatment, the prognosis for advanced-stage disease continues to be poor. One thriving area of research focuses on the use of epigenetic alterations for the diagnosis, prediction of treatment response, and prognosis of CRC. In this study, we evaluated original studies and meta-analyses published within the past five years to identify the most clinically relevant epigenetic biomarkers. DNA methylation-based assays, particularly those targeting and in stool and plasma, exhibit superior diagnostic accuracy compared to other epigenetic modalities. Circulating microRNAs (miRNAs), including miR-211, miR-197, and miR-21, as well as specific long non-coding RNAs (lncRNAs) such as SNHG14, LINC01485, and ASB16-AS1, also show promising diagnostic potential. Furthermore, panels combining multiple epigenetic markers, especially those incorporating DNA methylation targets, have demonstrated improved sensitivity and specificity for early-stage CRC detection. In the context of therapeutic prediction, microRNAs such as miR-140, miR-21, and miR-4442 have been associated with chemotherapy resistance and recurrence risk. DNA methylation markers like , and have also shown predictive value, while lncRNAs including MALAT1 and GAS6-AS1 remain less validated. Regarding prognosis, miRNAs appear to be the most promising biomarkers, with miR-675-5p and miR-150 being associated with poor survival, while miR-767-5p and miR-215 predict favorable outcomes. Methylation of , , and has been identified as an independent negative prognostic factor, while hypermethylation is linked to better prognosis. Selected lncRNAs, including THOR and LINC01094, have also demonstrated significant prognostic value. Despite these advances, challenges persist, including inconsistent reporting, limited external validation, and a lack of replication by independent research groups.