Evaluation of Epigenetic Silencing of the miR-139-5p gene in the pathogenesis of colorectal cancer and its diagnostic biomarker capability in plasma samples

Background : The pathogenesis of CRC requires primary genetic and epigenetic mechanisms including, methylation of CpG islands of the genes. In the current study, micro RNA-139-5p ( miR -139-5p) promoter methylated DNA was evaluated in tumor tissue and plasma samples from CRC affected patients. Methods: MiR -139-5p promoter methylation was investigated in 80 samples of tumoral tissue and healthy marginal tissue and the same number of plasma samples, using the MethyLight method. The miR-139-5p expression was assessed using the qPCR method. BT (Bioassay Technology) Elisa kit was applied to measure RAP-1b as a target gene of miR-139-5p. Results: Median PMR values of 12.4 (95% CI, 3.23-32.25) and 0.66 (95%CI, 0.51-1.0) were obtained from plasma samples of CRC patients and controls, sequentially. In plasma samples, the sensitivity and specificity of miR -139-5p promoter methylated marker were 75% and 92.5%, in the same order (AUC =0.958). Lower expression of miR-139-5p in plasma and tumor tissue of patients (P< 0.001) was shown. Also, a significant rise of RAP-1b protein concentration was observed in both mentioned specimens. Conclusion: Hyper-methylation of miR -139-5p could be suggested as high accuracy diagnostic biomarker for the detection of CRC in plasma samples.