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, pending further validation with large prospective studies.