Methods for generating a prognostic and/or subtype signature for a subject with pancreatic ductal adenocarcinoma (PDAC) are provided. In some embodiments, the methods include determining expression levels for one or more genes listed in Tables 2-5, 9, 10, or 11, and/or the DE-S and/or DE-T subset of genes in PDAC cells obtained from the subject, wherein the determining provides a prognostic and/or subtype signature for the subject. Also provided are methods for classifying a subject diagnosed with pancreatic ductal adenocarcinoma (PDAC) as having an activated stroma subtype or a normal stroma subtype of PDAC and/or a basal subtype or a classical subtype of PDAC; and methods for identifying a differential treatment strategy for a subject diagnosed with pancreatic ductal adenocarcinoma (PDAC).