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

Authors Sadegh Shesh Poli M, Khajeniazi S, Behnampour N, Kalani MR, Moradi A, Marjani A

Received 31 August 2019

Accepted for publication 22 January 2020

Published 11 February 2020 Volume 2020:12 Pages 973—980

DOI https://doi.org/10.2147/CMAR.S229397

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Seema Singh


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, Iran

Correspondence: Abdolvahab Moradi
Gastroenterology and Hepatology Research Center, Golestan University of Medical Sciences, Gorgan 4934174515, Iran
Tel +98 9111772107
Email abmoradi@yahoo.com
Abdoljalal Marjani
Metabolic Disorders Research Center, Department of Biochemistry and Biophysics, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Golestan Province 4934174515, Iran
Tel +98 171 4421651
Fax +98 171 4440225
Email abdoljalal@yahoo.com

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.

Keywords: miR-146a, cyclooxygenase-2, esophageal cancer

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