Genetic variants in NPAS2 gene and clinical outcomes of resectable non-small-cell lung cancer

Background: A series of studies have demonstrated that NPAS2 plays a critical role in the development and progression of several cancers. However, the association between genetic variants in the NPAS2 gene and the clinical outcome of patients with non-small-cell lung cancer (NSCLC) has not been investigated. Methods: Six functional SNPs in NPAS2 were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 484 Chinese NSCLC patients undergoing surgery. Multivariate Cox proportional hazards model were used for the prognosis analysis. Results: We found that SNP rs2305158 exhibited a significant association with overall survival of NSCLC patients in the dominant model (hazard ratio [HR]: 0.68; 95% CI: 0.49-0.95; p = 0.02). Lymph node metastasis was significantly associated with increased death risk (HR: 1.73; 95% CI: 1.24-2.40; p = 0.001) in patients with the homozygous wildtype (WW) genotype of rs2305158. However, no significant association was observed between them in patients carrying a heterozygous variant (WV) or homozygous variant (VV) genotype of rs2305158. Finally, in the joint and interaction analysis, the patients carrying homozygous wildtype (WW) genotype and lymph node metastasis from N1 to N3 conferred a significant increased effect on death (HR: 2.29; 95% CI: 1.40-3.76; p = 0.001). Conclusions: Our results suggest that NPAS2 polymorphisms may serve as an independent prognostic marker for NSCLC patients. Lay abstract Recently, the clinical significance of SNPs in patients with non-small-cell lung cancer (NSCLC) has become a research hotspot. In this study, we first demonstrated that NPAS2 gene polymorphisms could serve as an independent prognostic marker for NSCLC patients. Specifically, SNP rs2305158 was significantly associated with NSCLC overall survival. In addition, lymph node metastasis was significantly correlated with increased risk of death in patients with the homozygous wildtype (WW) genotype of rs2305158. Moreover, SNP rs2305158 interacts with lymph node metastasis stage and modulates the effects of lymph node metastasis stage on NSCLC death. The predictive role of SNPs in NPAS2 gene for clinical prognosis of NSCLC patients should be verified in larger clinical trials in the future.

Automated summary

This study suggests that NPAS2 gene polymorphisms may serve as an independent prognostic marker for NSCLC patients. Specifically, SNP rs2305158 is significantly associated with NSCLC overall survival, and lymph node metastasis is significantly correlated with increased risk of death in patients with the homozygous wildtype (WW) genotype of rs2305158. Additionally, SNP rs2305158 interacts with lymph node metastasis stage and modulates the effects of lymph node metastasis stage on NSCLC death.