Endothelial dysfunction markers in cervical cancer and their influence on patient outcome

BACKGROUND: Cervical cancer (CC) is a major cause of cancer-related mortality worldwide. Among CC patients, venous thromboembolism (VTE) represents the second leading cause of death, surpassed only by the malignancy itself. This life-threatening condition is characterised by blood stasis, heightened tendency for blood clotting (blood hypercoagulability), and endothelial dysfunction (ED). Single-nucleotide polymorphisms (SNPs) in ED-associated genes are believed to influence an individual’s susceptibility to VTE. Furthermore, these genetic variants may impact treatment response and long-term CC patient outcomes, given the close interaction between cancer and thrombosis. METHODS AND RESULTS: In this study, the implications of four ED-related SNPs were analysed in a cohort of 379 CC patients. The SNP NOS3 rs2070744 was significantly associated with the 10-year overall survival (OS) of young patients (≤ 49 years). In addition, this SNP was identified as a predictor of mortality risk in this subgroup, independent of CC stage (< IIB vs. ≥ IIB) and VTE status (yes vs. no) (CC vs. CT/TT; hazard ratio (HR) = 1.90, p = 0.025). Incorporating NOS3 rs2070744 into a predictive clinical model increased prognostic precision regarding patient survival by 15% compared to cancer stage alone. For the remaining SNPs, NOS3 rs1799983, vWF rs1063856 and SELP rs6136, no significant association with OS was detected (log-rank test, p > 0.05). CONCLUSION: These results underscore the role of NOS3 rs2070744 in CC patients and highlight the potential of integrating genetic markers into prognostic models to support personalised treatment strategies for these patients.