Determinant of Aggressive Phenotype in Metastatic Hormone-Sensitive Prostate Cancer Depends on an Intrinsic, Highly Aggressive Cell Cluster: Integrated Single-Cell RNA and Whole Transcriptomic Sequencing Analyses

作者：Minyong Kang, ByulA Jee, Jiwoong Yu, Soohyun Hwang, Kyunghee Park, Kyung Yeon Han, Wan Song, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Se Hoon Park, Woong‐Yang Park, Seong Soo Jeon · 发表于：Journal of Urologic Oncology · 年份：2025 · DOI：10.22465/juo.255000160008 · 被引用次数：1 · 研究领域：Prostate Cancer Treatment and Research、Cancer Immunotherapy and Biomarkers、Cancer Genomics and Diagnostics

Purpose: Although the combination of androgen deprivation therapy with docetaxel or abiraterone acetate and prednisone has become a standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC) and has shown improved overall survival, a subset of patients still progress to castration-resistant disease. However, the underlying molecular features in these patients remain poorly understood.Materials and Methods: We performed single-cell RNA sequencing (scRNA-seq) on 12 tissue samples, including 2 mHSPC samples, 7 primary prostate cancer (PCa) samples, and 3 matched normal samples from 7 patients. Raw sequencing data was processed by Cell Ranger software (10X Genomics) and aligned to the human reference genome (GRCh38). A comprehensive analysis of samples from patients with mHSPC was also conducted and validated using a cohort of 52 patients with mHSPC.Results: Our results identified distinct subpopulations within luminal and mononuclear phagocyte (MNP) clusters characterized by proliferative activation associated with unfavorable clinical outcomes. Furthermore, we observed that the MNP cluster exhibited significant proliferation activity. To understand the underlying mechanisms associated with aggressiveness, we conducted cell-cell interaction, copy number variation and pseudotime analysis. Utilizing 87 network genes from scRNA-seq, we classified 52 mHSPC patients into 2 molecular subtypes and demonstrated their correlation with distinct transcriptomic profiles and...