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.
British journal of cancer. 2024 Jul 12 [Epub ahead of print]
Bing-Biao Lin, Qingqing Huang, Binyuan Yan, Mingcheng Liu, Zhiqian Zhang, Hanqi Lei, Ronghua Huang, Jin-Tang Dong, Jun Pang
Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518000, China., Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Blvd, Shenzhen, 518055, China., The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515000, China., Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Blvd, Shenzhen, 518055, China. ., Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518000, China. .