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Chromatin remodeling restrains oncogenic functions in prostate cancer
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Journal Article
Chromatin remodeling restrains oncogenic functions in prostate cancer
2025
Overview
Primary prostate cancer presents with multifocal lesions and unpredictable clinical behavior, posing significant challenges for effective prognosis. To address this, we investigate the epigenomic landscape of prostate tumor biopsies from 25 treatment-naïve male patients by analyzing chromatin compartmentalization patterns. Our analysis reveals two distinct molecular subtypes: one with a Low Degree of Decompartmentalization (LDD) and another with a High Degree of Decompartmentalization (HDD). Here we show that the HDD subgroup exhibits extensive chromatin reorganization associated with diminished oncogenic potential. This subtype shows repression of molecular pathways involved in extracellular matrix remodeling and cellular plasticity. From this distinction, we derive an 18-gene transcriptional signature capable of differentiating HDD from LDD cases. Importantly, we validate the prognostic relevance of this signature in multiple independent cohorts totaling over 900 patients. Our findings suggest that epigenetic-derived signature at the time of diagnostic biopsy can offer a powerful tool for risk stratification in prostate cancer.
Prostate cancer (PCa) evaluation remains challenging due to its heterogenous and multifocal nature. Here, the authors reconstruct the nuclear chromatin compartmentalization of PCa patients-derived biopsies distinguishing two epigenetic subtypes and deriving an 18-gene signature with prognostic value on TCGA samples that is further validated with multiple independent PCa cohorts.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14
/ 38
/ 38/23
/ 38/39
/ 38/91
/ 45
/ Aged
/ Antigens
/ Biopsy
/ Chromatin Assembly and Disassembly - genetics
/ Gene Expression Regulation, Neoplastic
/ Genomes
/ Humanities and Social Sciences
/ Humans
/ Male
/ Patients
/ Prostatic Neoplasms - genetics
/ Prostatic Neoplasms - metabolism
/ Prostatic Neoplasms - pathology
/ Science
/ Tumors
