Thrombosis-related gene signature predicts prostate cancer recurrence and immune therapy: insights from retrospective cohorts, bioinformatics, and experimental validation.

Thrombosis was recognized as a significant cause of morbidity and mortality for prostate cancer (PCa). The potential mechanisms underlying the effect of thrombosis on PCa remain elusive. Retrospective analysis of dual-center clinical data identified thrombosis-PCa correlations. Bioinformatics integration of TCGA-PRAD transcriptomics and thrombosis-related genes enabled construction of a prognostic signature, validated externally. Functional, immune, and drug sensitivity analyses were performed. Experimental validation included IHC, qPCR, IF, in vitro functional assays, and in vivo models. Elevated thrombosis risk strongly correlated with PCa aggressiveness and adverse clinical features. A five-gene risk model stratified PCa patients into distinct survival groups (low-risk: superior outcomes), validated by ROC/Cox analyses as an independent prognostic tool. Findings from functional enrichment, alongside evaluations of immune cell infiltration, immunotherapy responsiveness, and drug sensitivity, reinforced the capacity to accurately forecast the clinical efficacy of precision therapies, as validated by clinical relevance analysis and nomogram development. Immunohistochemistry and qPCR of signature genes revealed marked differences between PCa and adjacent tissues. Importantly, experimental knockdown of VAV2 in 22RV1 cells downregulated prothrombotic inflammatory factors (CXCL8, IL-6, and VEGF). Conditioned media from VAV2-knockdown cells markedly inhibited tube formation in HUVECs and suppressed NETs formation. In vivo, mice administered with conditioned media from VAV2-deficient cells exhibited prolonged PT and APTT, and reduced fibrinogen levels, indicating attenuated coagulation potential. We successfully developed and validated an innovative and robust five-gene signature, seamlessly integrating clinical prognostic parameters for the precise prediction of PCa patients outcomes. This dissertation offers an in-depth exploration of thrombosis, elucidating potential biological mechanisms underpinning therapeutic strategies related to tumor immunity in PCa.