An immune-related microRNA signature prognostic model for pancreatic carcinoma and association with immune microenvironment

Abstract

Objective To establish a prognostic model based on immune-related microRNA (miRNA) for pancreatic carcinoma. Methods Weighted correlation network analysis (WGCNA) was performed using the "WGCNA" package to find the key module genes involved in pancreatic carcinoma. Spearman correlation analysis was conducted to screen immune-related miRNAs. Uni- and multi-variate COX regression analyses were carried out to identify miRNAs prognostic for overall survival (OS) of pancreatic carcinoma, which were then combined to generate a prognostic model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) analysis, distribution plot of survival status in patients and regression analysis were collectively performed to study the accuracy of the model in prognosis. Target genes of the miRNAs in the model were intersected with the key module genes, and a miRNA-mRNA network was generated and visualized by Cytoscape3.8.0. TIMER analysis was conducted to study the abundance of immune infiltrates in tumor microenvironment of pancreatic carcinoma. Expression levels of immune checkpoint genes in subgroups stratified by the model were compared by Wilcoxon test. Gene Set Enrichment Analysis (GSEA) was performed to analyze the enriched signaling pathways between subgroups. Results Differential analysis revealed 1,826 genes differentially up-regulated in pancreatic carcinoma and 1,276 genes differentially down-regulated. A total of 700 immune-related miRNAs were obtained, of which 7 miRNAs were significantly associated with OS of patients and used to establish a prognostic model with accurate predictive performance. There were 99 mRNAs overlapped from the 318 target genes of the 7 miRNAs and the key modules genes analyzed by WGCNA. Patient samples were categorized as high or low risk according to the prognostic model, which were significantly associated with dendritic cell infiltration and expression of immune checkpoint genes (TNFSF9, TNFRSF9, KIR3DL1, HAVCR2, CD276 and CD80). GSEA showed remarkably enriched signaling pathways in the two subgroups. Conclusion This study identified an immune-related 7-miRNA based prognostic model for pancreatic carcinoma, which could be used as a reliable tool for prognosis.