Polymorphisms in mitotic checkpoint-related genes can influence survival outcomes of early-stage non-small cell lung cancer

Abstract

This study was conducted to investigate the association between variants in mitotic checkpoint-related genes and clinical outcomes of non-small cell lung cancer (NSCLC). A total of 766 patients with NSCLC who underwent curative surgery were enrolled. Among the 73 variants evaluated, 4 variants were related with survival outcomes. BUB3 rs7897156C > T was associated with worse overall survival under a recessive model (adjusted hazard ratio = 1.58, 95% confidence interval = 1.07-2.33, P = 0.02). AURKB rs1059476G > A was associated with better overall survival under a recessive model (adjusted hazard ratio = 0.64, 95% confidence interval = 0.41- 0.99, P = 0.05). PTTG1 rs1895320T > C and RAD21 rs1374297C > G were associated with worse disease-free survival. In the functional study, relative luciferase activity was higher at the BUB3 rs7897156T allele compared to that at the C allele. Western blot showed that the phosphorylation of AKT and mTOR in the AURKB variant-type (M298) was significantly lower than in the AURKB wild-type (T298). We found that 4 variants of mitotic checkpoint-related genes were associated with survival outcomes in patients with surgically resected NSCLC. Particularly, our results suggest that BUB3 rs7897156C > T and AURKB rs1059476G > A are functional variants.