Potential four-miRNA signature associated with T stage and prognosis of patients with pancreatic ductal adenocarcinoma identified by co-expression analysis

With a 5-year survival rate of only 8%, pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-associated mortality worldwide. Unfortunately, even following radical surgery, patient outcomes remain poor. Emerging as a new class of biomarkers in human cancer, microRNAs (miRNAs/miRs) have been reported to have various tumor suppressor and oncogenic functions. In the present study, miRNA expression profiles of patients with PDAC and corresponding clinical data with survival profiles were obtained from The Cancer Genome Atlas database. A co-expression network was constructed to detect the modules significantly associated with clinical features by weighted gene co-expression network analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the hub miRNAs in the module of interest for functional annotation. A prognosis model consisting of hub miRNAs was generated using the R package ‘rbsurv’ and validated in survival analysis. The expression data of 523 miRNAs in 124 patients with PDAC were analyzed in a co-expression network. The turquoise module containing 131 miRNAs was identified to be associated with pathological T stage (cor=−0.21; P=0.02). The 39 hub miRNAs of the turquoise module were then detected using the ‘networkScreening’ function in R. These miRNAs were predominantly involved in biological processes including ‘regulation of transcription’, ‘apoptotic process’, ‘TGF-β receptor signaling pathway’, ‘Ras protein signal transduction’ and significantly enriched in ‘cell cycle’, ‘adherens junction’, ‘FoxO’, ‘Hippo’ and ‘PI3K-Akt signaling’ pathways. A prognostic signature consisting of four hub miRNAs (miR-1197, miR-218-2, miR-889 and miR-487a) associated with pathological T stage was identified to stratify the patients with early-stage PDAC into high and low risk groups. The signature may serve as a potential prognostic biomarker for patients with early-stage PDAC who undergo radical resection.