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<p>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.</p>

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Chromatin remodeling restrains oncogenic functions in prostate cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月16日

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  • Valentina Rosti,
  • Giovanni Lembo,
  • Cristiano Petrini,
  • Francesca Gorini,
  • Roberto Quadri,
  • Chiara Cordiglieri,
  • Margherita Mutarelli,
  • Elisa Salviato,
  • Elisabetta Casari,
  • Emanuele Di Patrizio Soldateschi,
  • Emanuele Montanari,
  • Giancarlo Albo,
  • Francesco Ripa,
  • Alessandra Fasciani,
  • Mariacristina Crosti,
  • Elisa De Lorenzis,
  • Marco Maggioni,
  • Valentina Vaira,
  • Maria Vivo,
  • Francesco Ferrari,
  • Chiara Lanzuolo

摘要

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.