ArticleBritish journal of cancer2024
An 18-gene signature of recurrence-associated endothelial cells predicts tumor progression and castration resistance in prostate cancer.
Article in British journal of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed.
- Integration of methylome and transcriptome reveals age-associated signatures of stage-specific dynamics and regulatory remodeling in dogs.GeroScience · 2026Article
- GABRD promotes hepatocellular carcinoma progression via the IL-10RA/JAK2-STAT3 signaling axis.Cell death & disease · 2026Article
- A Metabolic-Related Gene Signature for Predicting Biochemical Recurrence After Radical Prostatectomy: An Integrative Analysis and Targeted Therapeutic Validation.International journal of molecular sciences · 2026Article
- GABRD as an Emerging Oncogene: Exploring Functions and Therapeutic Implications Across Cancers.Life (Basel, Switzerland) · 2026Review
- The role of R-loop aberrations in lower-grade gliomas: prognostic, immune, and metabolic implications from multi-omics and machine learning analysis.Frontiers in immunology · 2026Article
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Abstract
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.
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