biostudies-literatureUnknown45(7)Ohara YNational Cancer InstituteNCI NIH HHSNational Institutes of HealthNIH HHSPancreatic ductal adenocarcinoma (PDAC) encompasses diverse molecular subtypes, including the classical/progenitor and basal-like/squamous subtypes, each exhibiting distinct characteristics, with the latter known for its aggressiveness. We employed an integrative approach combining transcriptome and metabolome analyses to pinpoint potential genes contributing to the basal-like/squamous subtype differentiation. Applying this approach to our NCI-UMD-German and a validation cohort, we identified LIM Domain Only 3 (LMO3), a transcription co-factor, as a candidate suppressor of the basal-like/squamous subtype. Reduced LMO3 expression was significantly associated with higher pathological grade, advanced disease stage, induction of the basal-like/squamous subtype and decreased survival among PDACCarcinogenesis475-486https://www.ebi.ac.uk/biostudies/studies/S-EPMC11229528biostudies-literatureLMO3 is a suppressor of the basal-like/squamous subtype and reduces disease aggressiveness of pancreatic cancer through glycerol 3-phosphate metabolism.PMC11229528Ohara YLiu HGaedcke JHussain SPAmbs SCraig AJDorsey THAzizian ACawley HYang SGhadimi MHanna NMoreno PfalseLMO3 is a suppressor of the basal-like/squamous subtype and reduces disease aggressiveness of pancreatic cancer through glycerol 3-phosphate metabolism.Pancreatic ductal adenocarcinoma (PDAC) encompasses diverse molecular subtypes, including the classical/progenitor and basal-like/squamous subtypes, each exhibiting distinct characteristics, with the latter known for its aggressiveness. We employed an integrative approach combining transcriptome and metabolome analyses to pinpoint potential genes contributing to the basal-like/squamous subtype differentiation. Applying this approach to our NCI-UMD-German and a validation cohort, we identified LIM Domain Only 3 (LMO3), a transcription co-factor, as a candidate suppressor of the basal-like/squamous subtype. Reduced LMO3 expression was significantly associated with higher pathological grade, advanced disease stage, induction of the basal-like/squamous subtype and decreased survival among PDAC2024-01-01T00:00:00Z2024 Jul2026-06-01T17:51:10.382Z2025-04-04T01:12:21.088ZS-EPMC112295283836663310.1093/carcin/bgae011