MicroRNA-146a as a prognostic biomarker for esophageal squamous cell carcinoma

Abstract

Background and Aims: MicroRNAs including miR146a have a regulatory role on the expression of genes and act with binding to 3ʹ-UTR region of the genes. Cyclooxygenase-2 (COX-2) is involved in carcinogenesis as an inflammatory marker, and microRNA-146a (miR-146a) as a negative regulatory factor. We aimed to evaluate miR146a expression as a prognostic or diagnostic biomarker for esophageal squamous cell carcinoma (ESCC) and also an association between miR146a and COX2 expression. Materials and Methods: We quantified the level of miR-146a and COX-2 expression in cancerous and adjacent normal tissue samples obtained from 34 patients with ESCC, using real-time�PCR. Statistical analyses were conducted using one-sample t-test. Receiver-operating characteristic (ROC) curve and Kaplan�Meier analysis were applied to assay miR146a as a diagnostic and prognostic marker, respectively, during 4 years of the study. Furthermore, the Cox regression model was performed to assay the hazard ratio (HR). The association between miR-146a and COX2 expression level in ESCC patients was evaluated by nonparametric Spearman�s rho analysis. Results: The results revealed a reduction of miR-146a expression in 50 of cancerous tissue when compared with adjacent normal regions (P-value=0.127). COX-2 expression in 80 of ESCC patients was higher than in the controls (P-value=0.001). Overall, in 60 of cases, direct association was seen between microRNA-146a and COX-2 expression level (correlation coefficient= 0.438, P-value=0.011). COX2 can be considered as a diagnostic biomarker (AUC=0.834, sensitivity=72, specificity =83, P-value<0.0001) but miR146a cannot be considered as a diagnostic biomarker (AUC=0.553, sensitivity=88, specificity =28, P-value=0.453). Survival analysis by Kaplan�Meier method showed miR146a and COX2 expression can be probably considered as prognostic biomarkers for ESCC because patients with high expression of miR146a had 7 months shorter life span and patients with low expression of COX2 had 8 months shorter life span. Conclusion: COX2 expression is a diagnostic biomarker. MiR-146a and COX2 expression can probably be considered as prognostic biomarkers for survival in ESCC. © 2020 Sadegh Shesh Poli et al