Abstract
Purpose
Several angiogenic prognostic markers are under investigation because of their potential clinical utility, aiming to improve patient outcomes. We hypothesized that genetic variant in the VEGF pathway could be used as prognostic markers of survival in non-small cell lung cancer (NSCLC) patients undergoing pulmonary resection.
Methods
We evaluated the relationship between genetic variants in the VEGF pathway and relapse-free survival (RFS, main endpoint) and overall survival (OS, secondary endpoint) among 131 patients with stage I–III NSCLC treated with surgical resection from 2009 to 2013. Clinical, pathological and surgical data were prospectively collected. Twenty-five variants in sixteen relevant genes were selected and genotyped in tumor samples by real time PCR. The Kaplan–Meier method with the log-rank test and Cox’s regression models were used for RFS and OS analyses.
Results
With a median follow-up of 36 (min = 2.8; max = 67.4) months, there were 31 (24%) relapses and 31 (24%) deaths. Overall, median RFS was not reached and median OS was 65 [95% confidence interval (CI) 56–75] months. The KRAS rs1137282 and PIK3C2A rs4356203 variants were significantly associated with RFS. For KRAS rs1137282, the 3-year RFS was 76% [95% CI 64–84%] in patients harboring an A/A genotype compared to 53% [95% CI 37–69%] in patients harboring an A/G or G/G genotype (p = 0.02). For PIK3C2A rs4356203, patients with an A/A or an A/G genotype had a 3-year RFS of 72% [95% CI 58–76%], whereas in patients with a G/G genotype was 49% [95% CI 28–70%] (p = 0.02). These associations remained statistically significant after adjusting for all the relevant clinical parameters in the multivariable analysis.
Conclusion
Genetic variants in VEGF pathway may be associated with recurrence in stage I–III NSCLC. Specifically, the KRAS rs1137282 could be considered as a prognostic factor for recurrence in resectable NSCLC patients. Although PIK3C2A rs4356203 was associated with RFS, further analyses are necessary to confirm these data.
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Acknowledgements
Ivana Sullivan has a Rio Hortega contract (CM13/00117) from the Instituto de Salud Carlos III. Madrid, Spain. This work was performed within the framework of the Doctorate of Medicine at the Autonomous University of Barcelona. The authors thank Carolyn Newey for English language editing.
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All procedures performed in this study were in accordance with the ethical standards of the institutional ethics committee and with the 1964 Helsinki declaration and its later amendments.
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I. Sullivan and J. Salazar contributed equally to this study.
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Sullivan, I., Salazar, J., Arqueros, C. et al. KRAS genetic variant as a prognostic factor for recurrence in resectable non-small cell lung cancer. Clin Transl Oncol 19, 884–890 (2017). https://doi.org/10.1007/s12094-017-1620-7
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DOI: https://doi.org/10.1007/s12094-017-1620-7