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Chromatin remodeling restrains oncogenic functions in prostate cancer

Author

Listed:
  • Valentina Rosti

    (National Research Council
    INGM Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”)

  • Giovanni Lembo

    (The AIRC Institute of Molecular Oncology)

  • Cristiano Petrini

    (The AIRC Institute of Molecular Oncology)

  • Francesca Gorini

    (INGM Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”)

  • Roberto Quadri

    (INGM Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”)

  • Chiara Cordiglieri

    (INGM Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”)

  • Margherita Mutarelli

    (National Research Council)

  • Elisa Salviato

    (The AIRC Institute of Molecular Oncology)

  • Elisabetta Casari

    (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    University of Milan)

  • Emanuele Di Patrizio Soldateschi

    (National Research Council
    INGM Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”)

  • Emanuele Montanari

    (University of Milan
    IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico)

  • Giancarlo Albo

    (University of Milan
    IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico)

  • Francesco Ripa

    (University of Milan)

  • Alessandra Fasciani

    (INGM Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”)

  • Mariacristina Crosti

    (INGM Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”)

  • Elisa Lorenzis

    (University of Milan
    IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico)

  • Marco Maggioni

    (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico)

  • Valentina Vaira

    (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    University of Milan)

  • Maria Vivo

    (Department of Chemistry and Biology “A. Zambelli”, University of Salerno)

  • Francesco Ferrari

    (The AIRC Institute of Molecular Oncology
    National Research Council)

  • Chiara Lanzuolo

    (National Research Council
    INGM Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”)

Abstract

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.

Suggested Citation

  • Valentina Rosti & Giovanni Lembo & Cristiano Petrini & Francesca Gorini & Roberto Quadri & Chiara Cordiglieri & Margherita Mutarelli & Elisa Salviato & Elisabetta Casari & Emanuele Di Patrizio Soldate, 2025. "Chromatin remodeling restrains oncogenic functions in prostate cancer," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64213-4
    DOI: 10.1038/s41467-025-64213-4
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