Identification of biomarkers for the prognosis of pancreatic ductal adenocarcinoma with miRNA microarray data.

Abstract The aim of this study was to explore the mechanism of chemotherapy resistance and to screen biomarkers of pancreatic ductal adenocarcinoma (PDAC). MicroRNA (miRNA) expression profile data for GSE38781 were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs between short-overall survival (OS) and long-OS patients were screened with the limma package in R. The function and protein-protein interaction (PPI) network of the miRNA target genes were further investigated. Finally, multivariate statistical analysis was performed to verify the significant miRNAs obtained in our work. In total, 66 miRNAs were identified to be differentially expressed. Gene ontology (GO) and pathway enrichment analysis showed that 163 miRNA target genes were mainly enriched in heart function, cancer development and angiogenesis. Ten nodes, including TGFBR1, TGFBR2, ACVR1 and SHC1, were found to be hub nodes in the PPI network. Multivariate statistical analysis showed 8 of the most significant miRNAs could completely distinguish the 2 groups of samples. Seven target genes (i.e., RET, ETS1, RHOA, NUMB, TIAM, ITGA5 and YY1) of the 8 significant miRNAs were found to be associated with control of cell fate decisions, T-cell lymphoma invasion and angiogenesis enhancement. The heart function-related pathway, cell cycle, immune system and angiogenesis may be dysregulated in patients with poorer prognosis. The significant nodes (e.g., TGFBR1, TGFBR2, ACVR1 and SHC1) in the PPI network may be potential biomarkers for predicting outcomes for patients with pancreatic cancer. The significant miRNAs and gene targets may be potential biomarkers or therapeutic targets for PDAC.