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

Abstract

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.

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