BackgroundPancreatic cancer (PC) remains one of the most lethal cancers. In contrast to the steady increase in survival for most cancers, the 5-year survival remains low for PC patients.MethodsWe describe a new pipeline that can be used to identify prognostic molecular biomarkers by identifying miRNA-mediated subpathways associated with PC. These modules were then further extracted from a comprehensive miRNA-gene network (CMGN). An exhaustive survival analysis was performed to estimate the prognostic value of these modules.ResultsWe identified 105 miRNA-mediated subpathways associated with PC. Two subpathways within the MAPK signaling and cell cycle pathways were found to be highly related to PC. Of the miRNA-mRNA modules extracted from CMGN, six modules showed good prognostic performance in both independent validated datasets.ConclusionsOur study provides novel insight into the mechanisms of PC. We inferred that six miRNA-mRNA modules could serve as potential prognostic molecular biomarkers in PC based on the pipeline we proposed.