Multi-dimensional analyses identify genes of high priority for pancreatic cancer research
Recommended Citation
Nwosu ZC, Giza H, Nassif M, Charlestin V, Menjivar RE, Kim D, Kemp SB, Sajjakulnukit P, Andren A, Zhang L, Lai WK, Loveless I, Steele NG, Hu J, Hu B, Wang S, Pasca di Magliano M, and Lyssiotis CA. Multi-dimensional analyses identify genes of high priority for pancreatic cancer research. JCI Insight 2025.
Document Type
Article
Publication Date
1-7-2025
Publication Title
JCI Insight
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a drug resistant and lethal cancer. Identification of the genes that consistently show altered expression across patients' cohorts can expose effective therapeutic targets and strategies. To identify such genes, we separately analyzed five human PDAC microarray datasets. We defined genes as 'consistent' if upregulated or downregulated in ≥ 4 datasets (adjusted P50%, to our knowledge, were uncharacterized in PDAC. These genes spanned multiple processes, including cell cycle, immunity, transport, metabolism, signaling and transcriptional/epigenetic regulation - cell cycle and glycolysis being the most altered. Several upregulated genes correlated with cancer features, and their suppression impaired PDAC cell viability in prior CRISPR/Cas9 and RNA interference screens. Further, the upregulated genes predicted sensitivity to bromodomain and extraterminal (epigenetic) protein inhibition, which, in combination with gemcitabine, disrupted amino acid metabolism and in vivo tumor growth. Our results highlight genes for further studies in the quest for PDAC mechanisms, therapeutic targets and biomarkers.
PubMed ID
39774001
ePublication
ePub ahead of print
