Chromatin remodeling restrains oncogenic functions in prostate cancer
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.
Authors
- Elisa Salviato (ORCID: https://orcid.org/0000-0003-3246-7820)
- Valentina Vaira (ORCID: https://orcid.org/0000-0003-4416-6216)
- Francesco Ripa (ORCID: https://orcid.org/0000-0002-7803-3879)
- Margherita Mutarelli (ORCID: https://orcid.org/0000-0002-2168-5059)
- Cristiano Petrini (ORCID: https://orcid.org/0000-0002-7727-7230)
- E. Montanari (ORCID: https://orcid.org/0000-0002-3586-666X)
- Roberto Quadri (ORCID: https://orcid.org/0000-0002-1553-2187)
- Francesca Gorini (ORCID: https://orcid.org/0000-0002-4619-6227)
- Alessandra Fasciani (ORCID: https://orcid.org/0000-0001-9127-4821)
- Chiara Lanzuolo (ORCID: https://orcid.org/0000-0003-2649-6334)
- Giancarlo Albo (ORCID: https://orcid.org/0000-0003-1979-3437)
- Marco Maggioni (ORCID: https://orcid.org/0000-0001-8603-8998)
- Francesco Ferrari (ORCID: https://orcid.org/0000-0002-9811-3753)
- Valentina Rosti
- Erminia Casari (ORCID: https://orcid.org/0000-0001-8899-1280)
- E. De Lorenzis (ORCID: https://orcid.org/0000-0002-5961-9874)
- Mariacristina Crosti (ORCID: https://orcid.org/0000-0001-8314-1391)
- Chiara Cordiglieri (ORCID: https://orcid.org/0000-0002-2013-0043)
- Maria Vivo (ORCID: https://orcid.org/0000-0003-2458-4226)
- Emanuele Di Patrizio Soldateschi (ORCID: https://orcid.org/0000-0002-3091-4386)
- Giovanni Lembo
Institutions
- University of Salerno (IT)
- University of Milan (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Ospedale Maggiore (IT)
- Institute of Applied Science and Intelligent Systems (IT)
- IFOM (IT)
- Istituto di Genetica Molecolare (IT)
- Institute of Biomedical Technologies (IT)
- National Research Council (IT)
- Istituto Nazionale Genetica Molecolare (IT)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-16
- DOI
- https://doi.org/10.1038/s41467-025-64213-4
- Primary Topic
- Prostate Cancer Treatment and Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00