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

## TL;DR

This study explores how genetic markers linked to endothelial dysfunction affect survival and treatment outcomes in cervical cancer patients.

## Contribution

The study identifies a specific genetic variant (NOS3 rs2070744) as a novel predictor of survival in young cervical cancer patients.

## Key findings

- The NOS3 rs2070744 SNP is significantly associated with 10-year overall survival in young cervical cancer patients.
- Including NOS3 rs2070744 in a clinical model improves survival prediction by 15% compared to cancer stage alone.
- Other SNPs (NOS3 rs1799983, vWF rs1063856, and SELP rs6136) were not significantly linked to survival outcomes.

## 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 (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).

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.