Chromatin remodeling restrains oncogenic functions in prostate cancer.

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-10-16 DOI:10.1038/s41467-025-64213-4

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

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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.

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染色质重塑抑制前列腺癌的致癌功能。

原发性前列腺癌多灶性病变，临床行为难以预测，对有效预后提出了重大挑战。为了解决这个问题，我们通过分析染色质区隔化模式，研究了25名treatment-naïve男性患者前列腺肿瘤活检的表观基因组景观。我们的分析揭示了两种不同的分子亚型：一种是低程度的分离（LDD），另一种是高程度的分离（HDD）。本研究表明，HDD亚群表现出广泛的染色质重组，与致癌潜力降低有关。该亚型显示参与细胞外基质重塑和细胞可塑性的分子途径受到抑制。从这个区别中，我们得出了一个18个基因的转录特征，能够区分HDD和LDD病例。重要的是，我们在超过900名患者的多个独立队列中验证了该特征的预后相关性。我们的研究结果表明，在诊断活检时，表观遗传学衍生的特征可以为前列腺癌的风险分层提供有力的工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.