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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1551815
This article is part of the Research Topic Immunoregulation in Urological Disorders: Novel Targets and Therapies View all 6 articles
New insights into Markers for Distinguishing Neuroendocrine Prostate Cancer: Evidence from Single-cell Analysis
Provisionally accepted
Hailang Luo 1,2
Chen Jin 1,2
Boyang Li 1,2 Meng Zhang 1,2
Zongyao Hao 1,2*
Qintao Ge 3,4*
Chaozhao Liang 1,2*- 1 Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- 2 Anhui Medical University, Hefei, Anhui Province, China
- 3 Shanghai Cancer Center, Fudan University, Shanghai, Shanghai Municipality, China
- 4 Fudan University, Shanghai, Shanghai Municipality, China
Background: Neuroendocrine prostate cancer (NEPC) is a highly aggressive malignancy with few effective treatment options. The identification of reliable biomarkers for NEPC is essential for early detection and intervention. Methods: We combined single-cell and bulk transcriptome analyzes to identify novel markers of NEPC. InferCNV to assess copy number variations, and leveraging consensus non-negative matrix factorization (cNMF) to characterize transcriptional programs. Pseudotime analysis was used to decipher prostate cancer (PCa) progression differentiation trajectory. BayesPrism integrates single-cell results and TCGA-PRAD sequencing information to further study prognostic features. Immunohistochemistry (IHC) was performed to validate the elevated expression of ASCL1 and WDFY4 in NEPC. Results: We identified five distinct expression programs of PCa malignant epithelial cells, where Module 3 presented NEPC expression patterns, with activation of DNA replication and cell cycle pathways and classical NEPC marker expression. Patients with high Module 3 proportion correlated to poor clinical outcomes, advanced Gleason scores, and higher T stages. Pseudotime analysis highlighted key trajectory-dependent genes involved 2 in the transition to NEPC, where expression of ASCL1 and WDFY4 elevated with progressing to NEPC cell fate, which were further comfirmed by IHC analysis, indicating that WDFY4 and ASCL1 might be novel potential markers for distinguishing NEPC. Conclusions: Combined single-cell and bulk analysis, we highlight the cellular heterogeneity and transcriptional programs, validated novel biomarkers of NEPC. Providing a foundation for early prediction of NEPC and management.
Keywords: Neuroendocrine prostate cancer (NEPC), single cell analysis, biomarker, WDFY4, ASCL1
Received: 26 Dec 2024; Accepted: 19 Feb 2025.
Copyright: © 2025 Luo, Jin, Li, Zhang, Hao, Ge and Liang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zongyao Hao, Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
Qintao Ge, Shanghai Cancer Center, Fudan University, Shanghai, 200032, Shanghai Municipality, China
Chaozhao Liang, Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
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