Abstract 7359: Priority targets in pancreatic cancer

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a drug resistant and lethal cancer. To better understand this disease, we separately analyzed five published human PDAC microarrays, determined the differential genes in each dataset and defined a gene as ‘consistent’ if it is ‘upregulated’ or ‘downregulated’ in >4 datasets (adjusted P<0.05). We identified 2,010 consistently upregulated- and 1,928 downregulated genes, over 50% of which were previously uncharacterized in PDAC. These genes span multiple processes, including cell cycle, immunity, transporters, metabolism, signaling, transcription factors and epigenetics. - with cell cycle and glycolysis being the most altered. Many consistent genes correlated with tumor subtype, proliferation, metastasis, and ~41% predicted survival, notably, OGN, PLOD2, DIAPH3, C2orf40, ADM, UPP1, ZNF189, DCBLD2, PLAG1, and glycolysis genesALDOA, GAPDH, PKM and LDHA. We identified 451 high priority targets, including 185 upregulated genes (notably in cell cycle and glycolysis) whose knockdown suppressed PDAC cell growth in prior RNAi screen studies. Our results represent an important milestone in the quest for mechanisms, drug targets and biomarkers and could enable the discovery of novel mechanisms and therapies in PDAC. Citation Format: Zeribe Chike Nwosu, Marina Pasca di Magliano, Costas Lyssiotis. Priority targets in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7359.