人们对前列腺癌 (PCa) 中内皮细胞 (EC) 异质性的预后和治疗意义知之甚少。我们在 8 个批量转录组和 4 个单细胞 RNA-seq 队列中研究了 EC 异质性与 PCa 复发和去势抵抗的关联。通过嵌套交叉验证比较 11 种机器学习算法，构建了循环相关 EC (RAEC) 签名。还测试了 RAEC 特异性基因的功能相关性。EC 的一个子集与原发性 PCa 的复发显着相关，并命名为 RAEC。 RAEC 具有尖端细胞和未成熟细胞的特征，并且富含迁移、血管生成和胶原蛋白相关途径。然后我们开发了代表 RAEC 的 18 基因 RAEC 特征 (RAECsig)。较高的 RAECsig 评分可独立预测肿瘤复发，并且与多个 PCa 队列中的临床病理因素和商业基因特征相比，表现更好或相当。在 18 个 RAECsig 基因中，FSCN1 在来自格里森评分较高的 PCa 的 EC 中表达上调； EC 中 FSCN1、TMEME255B 或 GABRD 的沉默会减弱管形成或抑制 PCa 细胞增殖。最后，较高的 RAECsig 评分可预测原发性前列腺癌和去势抵抗性前列腺癌的去势抵抗。这项研究建立了一个内皮特征，将 EC 子集与前列腺癌复发和去势抵抗联系起来。© 2024。作者。

The prognostic and therapeutic implications of endothelial cells (ECs) heterogeneity in prostate cancer (PCa) are poorly understood.We investigated associations of EC heterogeneity with PCa recurrence and castration resistance in 8 bulk transcriptomic and 4 single-cell RNA-seq cohorts. A recurrence-associated EC (RAEC) signature was constructed by comparing 11 machine learning algorithms through nested cross-validation. Functional relevances of RAEC-specific genes were also tested.A subset of ECs was significantly associated with recurrence in primary PCa and named RAECs. RAECs were characteristic of tip and immature cells and were enriched in migration, angiogenesis, and collagen-related pathways. We then developed an 18-gene RAEC signature (RAECsig) representative of RAECs. Higher RAECsig scores independently predicted tumor recurrence and performed better or comparably compared to clinicopathological factors and commercial gene signatures in multiple PCa cohorts. Of the 18 RAECsig genes, FSCN1 was upregulated in ECs from PCa with higher Gleason scores; and the silencing of FSCN1, TMEME255B, or GABRD in ECs either attenuated tube formation or inhibited PCa cell proliferation. Finally, higher RAECsig scores predicted castration resistance in both primary and castration-resistant PCa.This study establishes an endothelial signature that links a subset of ECs to prostate cancer recurrence and castration resistance.© 2024. The Author(s).