MicroRNAs and Other Small RNAs in Liquid Biopsies as Biomarkers for Early Detection of Colorectal Cancer

Early detection of colorectal cancer (CRC) is a major determinant of patient prognosis, as survival strongly depends on disease stage at diagnosis. Despite advances in screening programs, a significant proportion of CRC cases are still diagnosed at advanced stages, underscoring the need for improved early detection strategies. Most sporadic CRCs arise through the adenoma-carcinoma sequence over 10 to 15 years, providing a window for the detection of premalignant lesions, such as advanced adenomas. Current screening approaches are based on colonoscopy or its combination with stool-based tests. Although colonoscopy is the gold standard, it is an invasive technique with high associated costs and limited patient compliance. Stool-based tests are non-invasive and more widely accepted but lack specificity and sufficient sensitivity for detecting premalignant lesions. In this context, liquid biopsies have emerged as a promising minimally invasive alternative for identifying tumor-derived biomarkers in biological fluids such as blood or stool. Small non-coding RNAs (sncRNAs), and particularly microRNAs (miRNAs), have gained considerable attention as non-invasive biomarkers for their highly stability, resistance to handling conditions, and reliable quantification even in low-input samples. Single miRNAs and miRNA signatures detected in biofluids and combined with clinical parameters have shown promise for CRC detection. However, their utility for detecting advanced adenomas remains insufficiently characterized. Further validation in large, independent cohorts and standardization of analytical methods are required before their clinical implementation. Despite these challenges, sncRNA-based liquid biopsies represent a promising approach for improving early detection of CRC and, consequently, its prognosis.