Abstract
Background and MethodsEsophageal adenocarcinoma (EAC) is characterized by a steep rise in incidence rates in the Western population. The unique miRNA signature that distinguishes EAC from other upper gastrointestinal cancers remains unclear. Herein, we performed a comprehensive microarray profiling for the specific miRNA signature associated with EAC. We validated this signature by qRT-PCR.ResultsMicroarray analysis showed that 21 miRNAs were consistently deregulated in EAC. miR-194, miR-192, miR-200a, miR-21, miR-203, miR-205, miR-133b, and miR-31 were selected for validation using 46 normal squamous (NS), 23 Barrett’s esophagus (BE), 17 Barrett’s high grade dysplasia (HGD), 34 EAC, 33 gastric adenocarcinoma (GC), and 45 normal gastric (NG) tissues. The qRT-PCR analysis indicated that 2 miRNAs (miR-21 and miR-133b) were deregulated in both EAC and GC, and 6 miRNAs (up-regulated: miR-194, miR-31, miR-192, and miR-200a; down-regulated: miR-203 and miR-205) in EAC, as compared to BE but not in GC, indicating their potential unique role in EAC. Our data showed that miR-194, miR-192, miR-21, and miR-31 were up-regulated in BE adjacent to HGD lesions relative to isolated BE samples. Analysis of clinicopathological features indicated that down-regulation of miR-203 is significantly associated with progression and tumor stages in EAC. Interestingly, the overexpression levels of miR-194, miR-200a, and miR-192 were significantly higher in early EAC stages, suggesting that these miRNAs may be involved in EAC tumor development rather than progression.ConclusionOur findings demonstrate the presence of a unique miRNA signature for EAC. This may provide some clues for the distinct molecular features of EAC to be considered in future studies of the role of miRNAs in EAC and their utility as disease biomarkers.
Highlights
Upper gastrointestinal adenocarcinomas (UGCs), stomach and esophagus, are closely related in location and molecular profiles, they have distinct pathophysiological characteristics
Microarray analysis showed that 21 miRNAs were consistently deregulated in esophageal adenocarcinoma (EAC). miR-194, miR-192, miR-200a, miR-21, miR-203, miR-205, miR-133b, and miR-31 were selected for validation using 46 normal squamous (NS), 23 Barrett’s esophagus (BE), 17 Barrett’s high grade dysplasia (HGD), 34 EAC, 33 gastric adenocarcinoma (GC), and 45 normal gastric (NG) tissues
The Quantitative Real-Time PCR (qRT-PCR) analysis indicated that 2 miRNAs were deregulated in both EAC and GC, and 6 miRNAs in EAC, as compared to BE but not in GC, indicating their potential unique role in EAC
Summary
Upper gastrointestinal adenocarcinomas (UGCs), stomach and esophagus, are closely related in location and molecular profiles, they have distinct pathophysiological characteristics. These cancers are usually diagnosed at advanced stages where poor prognosis remains a common feature [1]. MiRNAs have gained significant attention because of their ability to regulate multiple oncogene and tumor suppressor signaling pathways [8,9] This fact has placed miRNA in the center of the cancer signaling network. We performed a comprehensive microarray profiling for the specific miRNA signature associated with EAC.
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