Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA, 94143, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, 94143, USA.
Nat Commun. 2022 Jan 10;13(1):141. doi: 10.1038/s41467-021-27322-4.
Prostate cancer is the second most common malignancy in men worldwide and consists of a mixture of tumor and non-tumor cell types. To characterize the prostate cancer tumor microenvironment, we perform single-cell RNA-sequencing on prostate biopsies, prostatectomy specimens, and patient-derived organoids from localized prostate cancer patients. We uncover heterogeneous cellular states in prostate epithelial cells marked by high androgen signaling states that are enriched in prostate cancer and identify a population of tumor-associated club cells that may be associated with prostate carcinogenesis. ERG-negative tumor cells, compared to ERG-positive cells, demonstrate shared heterogeneity with surrounding luminal epithelial cells and appear to give rise to common tumor microenvironment responses. Finally, we show that prostate epithelial organoids harbor tumor-associated epithelial cell states and are enriched with distinct cell types and states from their parent tissues. Our results provide diagnostically relevant insights and advance our understanding of the cellular states associated with prostate carcinogenesis.
前列腺癌是全球男性第二大常见恶性肿瘤，由肿瘤细胞和非肿瘤细胞类型混合组成。为了描述前列腺癌肿瘤微环境，我们对局限性前列腺癌患者的前列腺活检、前列腺切除术标本和患者来源的类器官进行了单细胞 RNA 测序。我们在前列腺上皮细胞中发现了具有高雄激素信号状态的异质细胞状态，这些状态在前列腺癌中富集，并鉴定出一群可能与前列腺癌发生相关的肿瘤相关 club 细胞。与 ERG 阳性细胞相比，ERG 阴性肿瘤细胞与周围腔上皮细胞表现出共同的异质性，并且似乎引起常见的肿瘤微环境反应。最后，我们表明前列腺上皮类器官含有肿瘤相关的上皮细胞状态，并且富含与其亲本组织不同的细胞类型和状态。我们的研究结果提供了具有诊断意义的见解，并推进了我们对与前列腺癌发生相关的细胞状态的理解。
