Methylation status of TRAF2 is associated with the diagnosis and prognosis of gastric cancer

The purpose was to investigate whether the expression level of TRAF2 gene was regulated by DNA methylation and explore the role of TRAF2 methylation in the diagnosis and prognosis of gastric cancer (GC). Firstly, we detected the expression of TRAF2 both at mRNA level and protein level. And the up-regulated of TRAF2 expression at two different levels were both found (P<0.001). Then we measured the methylated status of TRAF2 by MSP and got a result of that TRAF2 was hypomethylated in GC patients compared with healthy controls (P<0.001). Meanwhile, the relationship between TRAF2 methylation and clinicopathologic characteristics was estimated through chi-square. The outcome proved that TRAF2 methylation was impacted by age (P=0.024), lymph node metastasis (P=0.046), TNM stage (P=0.021), distant metastasis (P=0.002) and depth of invasion (P=0.002). The AUC of 0.795 accompanying a sensitivity of 66.7% and a specificity of 94.7% were obtained from Receiver Operating Characteristic (ROC) curve which indicated the diagnostic value of TRAF2 methylation was high. At last, we researched the prognostic value of TRAF2 methylation. Kaplan-Meier showed that patients with TRAF2 hypomethylation had lived much shorter than those with TRAF2 hypermethylation (log rank test, P<0.001). Cox regression analysis revealed TRAF2 hypomethylation (HR=18.827, 95% CI=3.103-114.222, P=0.001), lymph node metastasis (HR=0.154, 95% CI=0.047-0.512, P=0.002), distant metastasis (HR=3.032, 95% CI=1.116-8.237, P=0.030), as well as differentiation (HR=0.287, 95% CI=0.113-0.731, P=0.009) were all vital prognostic factors in GC. Taken together, TRAF2 expression was increased in GC patients by DNA hypomethylation and this methylation could be an independent diagnostic and prognostic indicator in GC.