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

Maryam Sadegh Shesh Poli,1 Safoura Khajeniazi,2 Nasser Behnampour,3 Mohammad Reza Kalani,4 Abdolvahab Moradi,5 Abdoljalal Marjani6 1School of New Technologies, Golestan University of Medical Sciences, Gorgan, Iran; 2Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran; 3Health Management and Social Development Research Center, Gorgan, Iran; 4Molecular Medicine Research Center, Golestan University of Medical Sciences, Gorgan, Iran; 5Gastroenterology and Hepatology Research Center, Golestan University of Medical Sciences, Gorgan, Iran; 6Abdoljalal Marjani Metabolic Disorders Research Center, Department of Biochemistry and Biophysics, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, IranCorrespondence: Abdolvahab MoradiGastroenterology and Hepatology Research Center, Golestan University of Medical Sciences, Gorgan 4934174515, IranTel +98 9111772107Email abmoradi@yahoo.comAbdoljalal MarjaniMetabolic Disorders Research Center, Department of Biochemistry and Biophysics, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Golestan Province 4934174515, IranTel +98 171 4421651Fax +98 171 4440225Email abdoljalal@yahoo.comBackground 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.Keywords: miR-146a, cyclooxygenase-2, esophageal cancer