Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Department of Urology, Weill Cornell Medicine, New York, NY, USA.
Nat Commun. 2020 Apr 24;11(1):1987. doi: 10.1038/s41467-020-15913-6.
Benign prostatic hyperplasia (BPH), a nonmalignant enlargement of the prostate, is among the most common diseases affecting aging men, but the underlying molecular features remain poorly understood, and therapeutic options are limited. Here we employ a comprehensive molecular investigation of BPH, including genomic, transcriptomic and epigenetic profiling. We find 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. At the epigenetic level, global hypermethylation is the dominant process. Integrating transcriptional and methylation signatures identifies two BPH subgroups with distinct clinical features and signaling pathways, validated in two independent cohorts. Finally, mTOR inhibitors emerge as a potential subtype-specific therapeutic option, and men exposed to mTOR inhibitors show a significant decrease in prostate size. We conclude that BPH consists of distinct molecular subgroups, with potential for subtype-specific precision therapy.
良性前列腺增生（BPH）是一种前列腺的非恶性增大，是影响老年男性的最常见疾病之一，但潜在的分子特征仍知之甚少，治疗选择也有限。在这里，我们采用了全面的分子研究方法来研究 BPH，包括基因组、转录组和表观遗传谱分析。我们没有发现 BPH 具有肿瘤特征的证据：没有驱动性基因组改变的证据，包括低编码突变率、与衰老组织一致的突变特征、最小的拷贝数改变，以及没有基因组重排。在表观遗传水平上，全局超甲基化是主要过程。整合转录和甲基化特征，确定了具有不同临床特征和信号通路的两个 BPH 亚组，在两个独立的队列中得到了验证。最后，mTOR 抑制剂作为一种潜在的亚型特异性治疗选择出现，而接受 mTOR 抑制剂治疗的男性前列腺体积明显缩小。我们得出结论，BPH 由不同的分子亚群组成，具有潜在的亚型特异性精确治疗的可能。
