Integrative genomic, transcriptomic, and epigenomic analyses of benign prostatic hyperplasia reveal new options for therapy
Integrative genomic, transcriptomic, and epigenomic analyses of benign prostatic hyperplasia reveal new options for therapy
Abstract Benign prostatic hyperplasia (BPH), a nonmalignant enlargement of the prostate, is one of the most common diseases affecting aging men, but the underlying molecular features of BPH remain poorly understood, and therapeutic options are limited. Here we employed a comprehensive molecular investigation of BPH, including genomic, transcriptomic and epigenetic profiling of 18 BPH cases. At the molecular level, we found no evidence of neoplastic features in BPH: no evidence of driver genomic alterations, including low coding mutation rates, mutational signatures consistent with aging tissues, minimal copy number alterations, and no genomic rearrangements. Similarly at the epigenetic level, we found global hypermethylation was the dominant process (unlike most neoplastic processes). By integrating transcriptional and methylation signatures, we identified two BPH subgroups with distinct clinical features and associated signaling pathways, which were validated in two independent cohorts. Finally, our analyses nominated mTOR inhibitors as a potential subtype-specific therapeutic option. Supporting this, a cohort of men exposed to mTOR inhibitors showed a significant decrease in prostate size. Our results demonstrate that BPH consists of distinct molecular subgroups, with potential for subtype-specific precision therapy via mTOR inhibition.
Redmond David、Fontugne Jacqueline、Pan Heng、Lee Daniel、Salari Keyan、Wang Zongwei、Romanel Alessandro、Lee Richard、Chughtai Bilal、Olumi Aria F.、Rubin Mark A.、Barbieri Christopher E.、Sboner Andrea、Liu Deli、Thomas Domonique、Vosoughi Aram、Shoag Jonathan、Goueli Ramy S.、Mosquera Juan Miguel、Elemento Olivier、Ravikumar Vaishali、Te Alexis、Demichelis Francesca、Poliak Daniel
Englander Institute for Precision Medicine of Weill Cornell Medicine and NewYork-Presbyterian HospitalEnglander Institute for Precision Medicine of Weill Cornell Medicine and NewYork-Presbyterian Hospital||Department of Pathology and Laboratory Medicine, Weill Cornell Medical CollegeEnglander Institute for Precision Medicine of Weill Cornell Medicine and NewYork-Presbyterian HospitalDepartment of Urology, Weill Cornell MedicineBeth Israel Deaconess Medical Center, Harvard Medical SchoolBeth Israel Deaconess Medical Center, Harvard Medical SchoolCentre for Integrative Biology, University of TrentoDepartment of Urology, Weill Cornell MedicineDepartment of Urology, Weill Cornell MedicineDepartment of Pathology and Laboratory Medicine, Weill Cornell Medical CollegeDepartment of Radiology, Weill Cornell Medicine||Department of BioMedical Research, University of Bern and InselspitalSandra and Edward Meyer Cancer Center, Weill Cornell Medicine||Department of Urology, Weill Cornell Medicine||Department of Radiology, Weill Cornell MedicineSandra and Edward Meyer Cancer Center, Weill Cornell Medicine||HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College||Department of Radiology, Weill Cornell Medicine||Department of Pathology and Laboratory Medicine, Weill Cornell Medical CollegeSandra and Edward Meyer Cancer Center, Weill Cornell Medicine||Department of Urology, Weill Cornell Medicine||HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College||Englander Institute for Precision Medicine of Weill Cornell Medicine and NewYork-Presbyterian HospitalDepartment of Urology, Weill Cornell MedicineDepartment of Pathology and Laboratory Medicine, Weill Cornell Medical CollegeSandra and Edward Meyer Cancer Center, Weill Cornell Medicine||Department of Urology, Weill Cornell MedicineDepartment of Urology, Weill Cornell MedicineHRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College||Department of Radiology, Weill Cornell Medicine||Englander Institute for Precision Medicine of Weill Cornell Medicine and NewYork-Presbyterian HospitalHRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College||Department of Radiology, Weill Cornell MedicineDepartment of Urology, Weill Cornell MedicineDepartment of Urology, Weill Cornell MedicineCentre for Integrative Biology, University of TrentoDepartment of Radiology, Weill Cornell Medicine
基础医学分子生物学医学研究方法
Redmond David,Fontugne Jacqueline,Pan Heng,Lee Daniel,Salari Keyan,Wang Zongwei,Romanel Alessandro,Lee Richard,Chughtai Bilal,Olumi Aria F.,Rubin Mark A.,Barbieri Christopher E.,Sboner Andrea,Liu Deli,Thomas Domonique,Vosoughi Aram,Shoag Jonathan,Goueli Ramy S.,Mosquera Juan Miguel,Elemento Olivier,Ravikumar Vaishali,Te Alexis,Demichelis Francesca,Poliak Daniel.Integrative genomic, transcriptomic, and epigenomic analyses of benign prostatic hyperplasia reveal new options for therapy[EB/OL].(2025-03-28)[2025-05-17].https://www.biorxiv.org/content/10.1101/805168.点此复制
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