Association between GPX3 promoter methylation and malignant tumors: A meta-analysis.

Glutathione peroxidase 3 (GPX3) has an important function of scavenging hydrogen peroxide and preventing cancer. The purpose of this meta-analysis was to analyze the relationship between GPX3 gene methylation and cancer and to further evaluate its diagnostic value for cancer. We screened eligible literatures from the PubMed, Embase, CNKI and Wanfang databases. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to measure the association of GPX3 methylation with cancer. Summary receiver operating characteristics (SROC) analysis was used to assess the diagnostic value of GPX3 methylation for cancer. A total of 17 eligible articles were included in the meta-analysis involving a total of 960 tumor samples and 445 non-tumor samples. The results showed that GPX3 hypermethylation was significantly associated with cancer (OR = 17.32, 95% CI = 8.22-36.51, P <  0.00001). Compared with cancer patients without lymph node metastasis, cancer patients with lymph node metastasis were more associated with GPX3 hypermethylation (OR = 2.97, 95% CI = 1.53-5.76, P =  0.001). SROC analysis showed for GPX3 methylation was a promising biomarker for cancer risk (AUC = 0.89, pooled sensitivity = 0.93, pooled specificity = 0.54, NLR = 0.15, PLR = 2.05, DOR = 17.32). TCGA database bioinformatics analysis of 696 pairs of tumor and non-tumor tissues further validate the association of GPX3 methylation with the risk of cancer [cg21504918: 0.10 (0.08, 0.15) vs. 0.09 (0.08, 0.11), P = 5.8E-28; cg26638444: 0.05 (0.04, 011) vs. 0.04 (0.03, 0.06), P = 8.7E-29]. In summary, our study indicates that GPX3 methylation is associated with cancer and has the potential to become a broad-spectrum tumor screening marker and has a value in predicting tumor lymph node metastasis.