CDHu40: a novel marker gene set of neuroendocrine prostate cancer.

Autor:	Liu S; Department of Medical and Molecular Genetics, Indiana University School of Medicine, 410 W 10th Street, Indianapolis, IN 46202, United States., Nam HS; Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, United States., Zeng Z; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre Dame, 100 Galvin Life Science Center, Notre Dame, IN 46556, United States., Deng X; Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, United States., Pashaei E; Department of Medical and Molecular Genetics, Indiana University School of Medicine, 410 W 10th Street, Indianapolis, IN 46202, United States., Zang Y; Department of Biostatistics & Health Data Science, Indiana University School of Medicine, 410 W 10th Street, Indianapolis, IN 46202, United States., Yang L; Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W Walnut St, Indianapolis, IN 46202, United States., Li C; Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1345 Center Dr Room P3-12, Gainesville, FL 32603, United States., Huang J; Department of Pathology, Duke University School of Medicine, Davison Building, 40 Duke Medicine, Durham, NC 27710, United States., Wendt MK; Department of Internal Medicine, Division of Hematology and Oncology, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242, United States.; Holden Comprehensive Cancer Center, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, United States., Lu X; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre Dame, 100 Galvin Life Science Center, Notre Dame, IN 46556, United States.; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, 535 Barnhill Dr, Indianapolis, IN 46202, United States., Huang R; Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, United States., Wan J; Department of Medical and Molecular Genetics, Indiana University School of Medicine, 410 W 10th Street, Indianapolis, IN 46202, United States.; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, 535 Barnhill Dr, Indianapolis, IN 46202, United States.; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 410 W 10th Street, Indianapolis, IN 46202, United States.
Jazyk:	angličtina
Zdroj:	Briefings in bioinformatics [Brief Bioinform] 2024 Sep 23; Vol. 25 (6).
DOI:	10.1093/bib/bbae471
Abstrakt:	Prostate cancer (PCa) is the most prevalent cancer affecting American men. Castration-resistant prostate cancer (CRPC) can emerge during hormone therapy for PCa, manifesting with elevated serum prostate-specific antigen levels, continued disease progression, and/or metastasis to the new sites, resulting in a poor prognosis. A subset of CRPC patients shows a neuroendocrine (NE) phenotype, signifying reduced or no reliance on androgen receptor signaling and a particularly unfavorable prognosis. In this study, we incorporated computational approaches based on both gene expression profiles and protein-protein interaction networks. We identified 500 potential marker genes, which are significantly enriched in cell cycle and neuronal processes. The top 40 candidates, collectively named CDHu40, demonstrated superior performance in distinguishing NE PCa (NEPC) and non-NEPC samples based on gene expression profiles. CDHu40 outperformed most of the other published marker sets, excelling particularly at the prognostic level. Notably, some marker genes in CDHu40, absent in the other marker sets, have been reported to be associated with NEPC in the literature, such as DDC, FOLH1, BEX1, MAST1, and CACNA1A. Importantly, elevated CDHu40 scores derived from our predictive model showed a robust correlation with unfavorable survival outcomes in patients, indicating the potential of the CDHu40 score as a promising indicator for predicting the survival prognosis of those patients with the NE phenotype. Motif enrichment analysis on the top candidates suggests that REST and E2F6 may serve as key regulators in the NEPC progression. (© The Author(s) 2024. Published by Oxford University Press.)
Databáze:	MEDLINE
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