Journal article
CDHu40: a novel marker gene set of neuroendocrine prostate cancer
Briefings in bioinformatics, Vol.25(6), bbae471
11/2024
DOI: 10.1093/bib/bbae471
PMCID: PMC11422505
PMID: 39318189
Abstract
Abstract 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.
Details
- Title: Subtitle
- CDHu40: a novel marker gene set of neuroendocrine prostate cancer
- Creators
- Sheng Liu - Indiana University – Purdue University IndianapolisHye Seung Nam - Purdue University West LafayetteZiyu Zeng - University of Notre DameXuehong Deng - Purdue University West LafayetteElnaz Pashaei - Indiana University – Purdue University IndianapolisYong Zang - Indiana University – Purdue University IndianapolisLei Yang - Indiana University School of MedicineChenglong Li - Florida CollegeJiaoti Huang - Duke UniversityMichael K Wendt - University of IowaXin Lu - University of Notre DameRong Huang - Purdue University SystemJun Wan - Indiana University – Purdue University Indianapolis
- Resource Type
- Journal article
- Publication Details
- Briefings in bioinformatics, Vol.25(6), bbae471
- Publisher
- OXFORD UNIV PRESS
- DOI
- 10.1093/bib/bbae471
- PMID
- 39318189
- PMCID
- PMC11422505
- ISSN
- 1467-5463
- eISSN
- 1477-4054
- Grant note
- National Institutes of Health (NIH): R01CA248033, R01 HL147871 U.S. Army Medical Research Acquisition Activity, Prostate Cancer Research Program: W81XWH-13-1-0398, W81XWH-16-1-0394, W81XWH-22-1-0332 American Heart Association: AHA TPA 969255 Indiana University Simon Comprehensive Cancer Center (IUSCCC): NIH/NCI P30CA082709
This work was partially supported by the grants from the National Institutes of Health (NIH, R01CA248033 to XL, R01 HL147871 to L.Y.), the U.S. Army Medical Research Acquisition Activity, Prostate Cancer Research Program (W81XWH-13-1-0398 to C.D.H., W81XWH-16-1-0394 to C.D.H., and W81XWH-22-1-0332 to R.H.), American Heart Association (AHA TPA 969255 to L.Y.), Indiana University Simon Comprehensive Cancer Center (IUSCCC, NIH/NCI P30CA082709), the Near-Miss Initiative at IUSCCC to J.W., the Showalter Scholar program funded by Ralph W. and Grace M. Showalter Research Trust Fund to J.W. and L.Y., independently, and additional support from the Walther Cancer Foundations.
- Language
- English
- Electronic publication date
- 09/23/2024
- Date published
- 11/2024
- Academic Unit
- Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984719237602771
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