Increased Levels of miR-15b-5p and miR-20b-5p in Pancreatic Ductal Adenocarcinoma with Hepatic Metastases

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal forms of cancer. The symptoms appear in advanced stages, and diagnostic and prognostic tests for the early detection of PDAC and disease evolution are not available. The dysregulation of microRNAs (miRNAs) has been associated with cancer development and progression, and some miRNAs have been reported to promote specific metastasis. In this study we aimed to identify the miRNAs dysregulated in PDAC tumoral tissues and a subset of miRNAs associated with tumoral characteristics, mainly metastasis presence and site. For this, the expression of 84 miRNAs was evaluated by qPCR in 30 tumoral tissues and 16 samples of non-tumoral pancreatic tissues. The comparison revealed 32 dysregulated miRNAs (19 upregulated and 13 downregulated) in the PDAC group. Reactome pathway over-representation analysis revealed that these miRNAs are involved in several biological pathways, including “ESR-mediated signaling”, “PIP3 activates AKT signaling”, and “Regulation of PTEN”, among others. Moreover, our study identified an upregulation of miR-15b-5p and miR-20b-5p in the tumoral tissues of patients with hepatic metastasis, outlining these miRNAs as potential markers for hepatic metastasis. No significant difference in miRNA expression was observed in relation to anatomic location, lymphovascular invasion, lung metastasis, and the presence of diabetes.