MicroRNA in the Pathogenesis and Prognosis of Esophageal Cancer

Jian      Gu; Yan      Wang; Xifeng      Wu

Abstract

Esophageal cancer (EC) is a deadly disease. EC usually occurs as either adenocarcinoma (EAC) or squamous cell carcinomas (ESCC). The development of EAC generally follows the metaplasia-dysplasia-carcinoma sequence. Barrett’s esophagus (BE) is a metasplastic precursor of EAC. Multiple global miRNA expression profiling and candidate gene studies have been performed in EAC and ESCC that clearly support the important roles of miRNAs in the pathogenesis of EAC and ESCC. A number of consistently dysregulated miRNAs have been identified in EAC and/or ESCC, including upregulation of miR-21, miR-192, miR-194, miR-106-25 polycistron (miR-25, miR-93, and miR-106b), miR-10b, miR-151, and miR-93, and downregulation of miR-375, miR-203, miR-205, miR-145, miR- 27b, miR-100, miR-125b, let-7c, etc. Most of these miRNAs are also dysregulated in other cancer types and their target genes have been extensively studied in different cancers. The prognostic value of miR-21 and miR-375 has been replicated in independent studies. Circulating miRNAs as potential biomarkers for early detection, prognosis, and treatment response have only been scarcely studied in EC. The association of genetic variations in miRNA regulatory pathway with EC risk or outcome is a largely uncharted territory. Future studies should be focused on the role of miRNAs in the prognosis of EC, the identification of circulating miRNAs and miRNA-related genetic variations as biomarkers in EC, and the biological mechanisms underlying the contribution of miRNA dysreguation to EC. A better understanding of roles of miRNA in EC developemnt may provide new avenues for the early detection, diagnosis, prognosis, and therapy of this deadly disease.

Keywords: microRNA, esophageal cancer, Barrett's esophagus, early detection, prognosis, circulating biomarker, adenocarcinoma (EAC), squamous cell carcinomas, miR-21, miR-375