An 18-gene signature of recurrence-associated endothelial cells predicts tumor progression and castration resistance in prostate cancer

Lin, Bing-Biao1,2,3; Huang, Qingqing2; Yan, Binyuan1; Liu, Mingcheng2; Zhang, Zhiqian2; Lei, Hanqi1; Huang, Ronghua4; Dong, Jin-Tang2; Pang, Jun1

2024-07-01

10.1038/s41416-024-02761-0

BRITISH JOURNAL OF CANCER   影响因子和分区

0007-0920

1532-1827

BackgroundThe prognostic and therapeutic implications of endothelial cells (ECs) heterogeneity in prostate cancer (PCa) are poorly understood.MethodsWe 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.ResultsA 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.ConclusionThis study establishes an endothelial signature that links a subset of ECs to prostate cancer recurrence and castration resistance.

SCI

英语

通讯

Oncology

Oncology

WOS:001270077900001

SPRINGERNATURE

CLINICAL MEDICINE

Web of Science

1.Sun Yat Sen Univ, Affiliated Hosp 7, Kidney & Urol Ctr, Dept Urol,Pelv Floor Disorders Ctr, Shenzhen 518000, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Sch Med, Dept Human Cell Biol & Genet, 1088 Xueyuan Blvd, Shenzhen 518055, Peoples R China
3.Shantou Univ, Canc Hosp, Med Coll, Dept Radiotherapy, Shantou 515041, Guangdong, Peoples R China
4.Shantou Univ, Affiliated Hosp 1, Med Coll, Shantou, Guangdong, Peoples R China

Lin, Bing-Biao,Huang, Qingqing,Yan, Binyuan,et al. An 18-gene signature of recurrence-associated endothelial cells predicts tumor progression and castration resistance in prostate cancer[J]. BRITISH JOURNAL OF CANCER,2024.

Lin, Bing-Biao.,Huang, Qingqing.,Yan, Binyuan.,Liu, Mingcheng.,Zhang, Zhiqian.,...&Pang, Jun.(2024).An 18-gene signature of recurrence-associated endothelial cells predicts tumor progression and castration resistance in prostate cancer.BRITISH JOURNAL OF CANCER.

Lin, Bing-Biao,et al."An 18-gene signature of recurrence-associated endothelial cells predicts tumor progression and castration resistance in prostate cancer".BRITISH JOURNAL OF CANCER (2024).