Determinant of aggressive phenotype in metastatic hormone sensitive prostate cancer depends on an intrinsic, highly aggressive cell cluster: Integrated single- cell and whole transcriptomic analyses

Abstract

Abstract Several studies have reported that prostate cancer has a relatively favorable prognosis; however, patients with locally advanced and metastatic disease have significantly low 10-year survival rates. Although the combination of androgen deprivation therapy with docetaxel or abiraterone acetate and prednisone has become the standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC), and improved overall survival, a subset of patients is prone to developing castration-resistant prostate cancer. Furthermore, the underlying mechanisms governing treatment response in these patients remain poorly understood. The objective of this study was to identify aggressive cell types in patients with mHSPCs with poor clinical outcomes. A comprehensive analysis of samples from patients with mHSPC was conducted and validated using a cohort of 52 patients with mHSPC. Our results identified a distinct subtype characterized by proliferative activation associated with unfavorable clinical outcomes. A novel 14-gene signature serving as a predictive marker for survival outcomes was developed to facilitate prognosis and guide treatment decisions, particularly in patients with mHSPC. This study provides valuable insights into the identification of high-risk patients, novel biomarkers, and potential therapeutic targets for individuals with mHSPC. Furthermore, the results in this study can serve as a basis for future investigations aimed at refining prognostic strategies and developing targeted therapies for patients with mHSPC.