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CDHu40: a novel marker gene set of neuroendocrine prostate cancer (NEPC)
Preprint   Open access

CDHu40: a novel marker gene set of neuroendocrine prostate cancer (NEPC)

Sheng Liu, Hye Seung Nam, Ziyu Zeng, Xuehong Deng, Elnaz Pashaei, Yong Zang, Lei Yang, Chenglong Li, Jiaoti Huang, Michael K Wendt, …
bioRxiv : the preprint server for biology
Cold Spring Harbor Laboratory
03/31/2024
DOI: 10.1101/2024.03.28.587205
PMCID: PMC10996696
PMID: 38585861
url
https://doi.org/10.1101/2024.03.28.587205View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

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 (PSA) 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 (AR) signaling and a particularly unfavorable prognosis. In this study, we incorporated computational approaches based on both gene expression profiles and protein-protein interaction (PPI) networks. We identified 500 potential marker genes, which are significantly enriched in cell cycle and neuronal processes. The top 40 candidates, collectively named as CDHu40, demonstrated superior performance in distinguishing NE prostate cancer (NEPC) and non-NEPC samples based on gene expression profiles compared to other published marker sets. Notably, some novel 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. our study integrates gene expression variances in multiple NEPC studies and protein-protein interaction network to pinpoint a specific set of NEPC maker genes namely CDHu40. These genes and scores based on their gene expression levels effectively distinguish NEPC samples and underscore the clinical prognostic significance and potential mechanism.

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