Updated project metadata. This project is reporting on microdissection proteomics of human operable, non-neoadjuvant treated pancreatic ductal adenocarcinomas (PDAC) with deep coverage of histologically neoplastic and adjacent healthier exocrine glands as well as stromal regions surrounding both. Through proteomic analysis, the parenchymal sample types differed significantly, with the malignant regions characterized by a broad downregulation of digestive enzymes. Instead, the stromal areas were alike, dominated by extracellular matrix proteins and lower expression of most metabolic pathways compared to the exocrine areas. Cholesterol synthesizing enzymes were more abundant in the tumor than stroma, as confirmed by an independent PDAC dataset and immunohistochemistry of PDAC microarrays. However, this was not accompanied by intratumor lipid deposition. Pathways most prognostic for survival were unexpectedly enriched in the histologically healthier exocrine glands, with a specific prognostic marker. Systematic analysis of pancreatic cancer transcriptomes from The Cancer Genome Atlas revealed that increased transcriptional complexity confers poor prognosis in PDAC.