WDR74 rs11231247 contributes to the susceptibility and prognosis of non-small cell lung cancer.

OBJECTIVES

WD repeat-containing protein 74 (WDR74) has been linked with the development of lung cancer. This study aims to investigate the relationship between WDR74 rs11231247 and non-small cell lung cancer (NSCLC) susceptibility and the prognosis of NSCLC patients.

METHODS

UALCAN, MethPrimer, ensembl and Pancan meQTL databases were used for bioinformatics analysis. The case-control study included 462 NSCLC patients and 462 health controls. WDR74 rs11231247 genotype was determined by PCR-RFLP. Logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (95% CI) for analyzing the association of WDR74 SNP with the risk of NSCLC. Log-rank test and Cox regression analysis were used to evaluate the effect of WDR74 genetic variation on the prognosis of NSCLC.

RESULTS

Compared with normal tissues, WDR74 expression level was higher and methylation level was lower in LUAD tissues. There were two CpG islands presented in the promoter of WDR74. And rs11231247 was in the second CpG island. We then discovered that rs11231247 CC and CT were more likely modified by methylation. LUAD case-control study demonstrated that rs11231247 CC genotype was associated with NSCLC risk with OR (95%CI) of 5.29 (2.59-10.79). Stratified analysis showed that rs11231247 T > C polymorphism could increase NSCLC risk in younger subjects (age≤58) (OR = 1.64, 95%CI = 1.06-2.54, P = 0.027). Survival analysis and Cox regression analysis showed rs11231247 CC genotype contributed to a poor prognosis of NSCLC patients (MST=21, HR=2.09, 95%CI=1.17-3.75).

CONCLUSION

WDR74 rs11231247 polymorphism affected the risk and prognosis of NSCLC.