MicroRNA-146a as a Prognostic Biomarker for Esophageal Squamous Cell Carcinoma

• Published in: Cancer management and research Vol. 12; pp. 973 - 980
• Main Authors: Sadegh Shesh Poli, Maryam, Khajeniazi, Safoura, Behnampour, Nasser, Kalani, Mohammad Reza, Moradi, Abdolvahab, Marjani, Abdoljalal
• Format: Journal Article
• Language: English
• Published: New Zealand Dove 01.01.2020; Dove Medical Press
• Subjects: cyclooxygenase-2; esophageal cancer; mir-146a; Original Research; miR-146a; esophageal cancer; cyclooxygenase-2
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S229397

MicroRNAs including miR146a have a regulatory role on the expression of genes and act with binding to 3'-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. 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 -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. The results revealed a reduction of miR-146a expression in 50% of cancerous tissue when compared with adjacent normal regions ( value=0.127). COX-2 expression in 80% of ESCC patients was higher than in the controls ( value=0.001). Overall, in 60% of cases, direct association was seen between microRNA-146a and COX-2 expression level (correlation coefficient= 0.438, value=0.011). COX2 can be considered as a diagnostic biomarker (AUC=0.834, sensitivity=72%, specificity =83%, -value<0.0001) but miR146a cannot be considered as a diagnostic biomarker (AUC=0.553, sensitivity=88%, specificity =28%, -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. COX2 expression is a diagnostic biomarker. MiR-146a and COX2 expression can probably be considered as prognostic biomarkers for survival in ESCC.