Prostate cancer shows remarkable clinical heterogeneity, which manifests in spatial and clonal genomic diversity. By contrast, the transcriptomic heterogeneity of prostate tumours is poorly understood. Here we have profiled the transcriptomes of 36,424 single cells from 13 prostate tumours and identified the epithelial cells underlying disease aggressiveness. The tumour microenvironment (TME) showed activation of multiple progression-associated transcriptomic programs. Notably, we observed promiscuous KLK3 expression and validated the ability of cancer cells in altering T-cell transcriptomes. Profiling of a primary tumour and two matched lymph nodes provided evidence that KLK3 ectopic expression is associated with micrometastases. Close cell–cell communication exists among cells. We identified an endothelial subset harbouring active communication (activated endothelial cells, aECs) with tumour cells. Together with sequencing of an additional 11 samples, we showed that aECs are enriched in castration-resistant prostate cancer and promote cancer cell invasion. Finally, we created a user-friendly web interface for users to explore the sequenced data.

前列腺癌表现出显着的临床异质性，表现为空间和克隆基因组多样性。相比之下，人们对前列腺肿瘤的转录组异质性知之甚少。在这里，我们分析了来自 13 个前列腺肿瘤的 36,424 个单细胞的转录组，并鉴定了潜在疾病侵袭性的上皮细胞。肿瘤微环境 (TME) 显示多个进展相关转录组程序的激活。值得注意的是，我们观察到混杂的KLK3表达并验证了癌细胞改变 T 细胞转录组的能力。原发肿瘤和两个匹配的淋巴结的分析提供了KLK3的证据异位表达与微转移有关。细胞间存在细胞间的紧密通讯。我们确定了一个内皮亚群，该亚群与肿瘤细胞具有活跃的通讯（激活的内皮细胞，aEC）。连同另外 11 个样本的测序，我们发现 aECs 在去势抵抗性前列腺癌中富集并促进癌细胞侵袭。最后，我们创建了一个用户友好的 Web 界面，供用户探索测序数据。