Identification of microRNA biomarkers for the early detection and differential diagnosis of colorectal cancer

Introduction. Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality in both men and women. Early detection is crucial for improving patient outcomes; however, currently available screening methods are often invasive and demonstrate suboptimal diagnostic accuracy, limiting their applicability in the general population. In recent years, microRNAs (miRNAs) have attracted considerable attention as promising biomarkers for early CRC detection, with potential clinical implementation that may contribute to reduced mortality.

Aim. To analyze miRNA expression in tissues of patients with colorectal cancer and colorectal adenomas in order to identify promising biomarkers for the development of diagnostic tools for CRC.

Materials and methods. The study was performed using archival formalin-fixed paraffin-embedded colon tissue samples. Total RNA, including small RNAs, was isolated following enrichment of the target epithelium by microdissection. Expression levels of miR-21-5p, -23a-3p, -92a-3p, -17-5p, -451a, -1246, 135b-5p, and the reference -210-3p were analyzed using the stem-loop detection method. Relative expression was calculated using the –ΔΔCt method. Statistical significance of intergroup differences was assessed using the Mann–Whitney U test, while diagnostic performance was evaluated by ROC analysis with calculation of area under the curve (AUC), sensitivity, and specificity.

Results. MiR-17-5p, -21-5p, -92a-3p, -135b-5p, and -1246 demonstrated high diagnostic potential, with expression levels significantly elevated in adenomas and adenocarcinomas compared with conditionally normal epithelium. MiR-17-5p was of particular interest, as its intermediate expression level in adenomas suggests involvement in the early stages of tumor progression. In ROC analysis, miR-17-5p demonstrated high sensitivity and specificity both for differentiating CRC from normal tissue and for distinguishing adenomas from adenocarcinomas. In addition, miR-17-5p and miR-23a-3p effectively differentiated adenomas from both normal and tumor tissues.

Conclusion. The identified miRNAs, particularly miR-17-5p, -21-5p, -92a-3p, -135b-5p, and -1246, represent a promising basis for the development of diagnostic miRNA panels. Further investigation of tissue and extracellular levels of these miRNAs may facilitate the development of minimally invasive diagnostic and monitoring tests for CRC and colorectal adenomas, as well as enable evaluation of the prognostic significance of these biomarkers.