Roudier Martine P, Gulati Roman, Sayar Erolcan, Patel Radhika A, Tratt Micah, Richards Helen M, Cejas Paloma, Munoz Gomez Miguel, Qiu Xintao, Xie Yingtian, Hanratty Brian, Zaidi Samir, Zhao Jimmy L, Adil Mohamed, Mittal Chitvan, Zhao Yibai, Dumpit Ruth, Coleman Ilsa, Low Jin-Yih, Persse Thomas, Galipeau Patricia, Lee John K, Tretiakova Maria, Chambers Meagan, Vakar-Lopez Funda, True Lawrence D, Perrone Marie, Lam Hung-Ming, Kollath Lori A, Ding Chien-Kuang Cornelia, Harmon Stephanie, Cheng Heather H, Yu Evan Y, Montgomery Robert B, Hawley Jessica E, Lin Daniel W, Corey Eva, Schweizer Michael T, Setty Manu, Ha Gavin, Sawyers Charles L, Morrissey Colm, Long Henry, Nelson Peter S, Haffner Michael C
Department of Urology, University of Washington, Seattle, Washington, USA.
Division of Public Health Sciences and.
J Clin Invest. 2025 Jun 10;135(15). doi: 10.1172/JCI186599. eCollection 2025 Aug 1.
Metastatic prostate cancer (mPC) is a clinically and molecularly heterogeneous disease. While there is increasing recognition of diverse tumor phenotypes across patients, less is known about the molecular and phenotypic heterogeneity present within an individual. In this study, we aimed to define the patterns, extent, and consequences of inter- and intratumoral heterogeneity in lethal prostate cancer. By combining and integrating in situ tissue-based and sequencing approaches, we analyzed over 630 tumor samples from 52 patients with mPC. Our efforts revealed phenotypic heterogeneity at the patient, metastasis, and cellular levels. We observed that intrapatient intertumoral molecular subtype heterogeneity was common in mPC and showed associations with genomic and clinical features. Additionally, cellular proliferation rates varied within a given patient across molecular subtypes and anatomic sites. Single-cell sequencing studies revealed features of morphologically and molecularly divergent tumor cell populations within a single metastatic site. These data provide a deeper insight into the complex patterns of tumoral heterogeneity in mPC with implications for clinical management and the future development of diagnostic and therapeutic approaches.
转移性前列腺癌(mPC)是一种临床和分子层面均具有异质性的疾病。虽然人们越来越认识到不同患者之间存在多种肿瘤表型,但对于个体内部存在的分子和表型异质性却知之甚少。在本研究中,我们旨在明确致命性前列腺癌瘤间和瘤内异质性的模式、程度及后果。通过结合并整合基于原位组织和测序的方法,我们分析了来自52例mPC患者的630多个肿瘤样本。我们的研究结果揭示了患者、转移灶和细胞水平上的表型异质性。我们观察到,患者体内瘤间分子亚型异质性在mPC中很常见,并且与基因组和临床特征相关。此外,在给定患者中,不同分子亚型和解剖部位的细胞增殖率有所不同。单细胞测序研究揭示了单个转移灶内形态和分子特征不同的肿瘤细胞群体的特征。这些数据为mPC中肿瘤异质性的复杂模式提供了更深入的见解,对临床管理以及诊断和治疗方法的未来发展具有重要意义。