Endothelial Dysfunction Markers in Cervical Cancer and their Influence on Patient Outcome

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Abstract

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. 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 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 CC staging 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). 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.

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