Hypermethylated GPR135 gene expression is a favorable independent prognostic factor in nasopharyngeal carcinoma

Abstract

Abstract Purpose To investigate the methylation status and expression level of G protein-coupled receptor 135 (GPR135) in nasopharyngeal carcinoma (NPC) and determine its prognostic value. Methods The GPR135 methylation data of NPC and normal nasopharyngeal tissues were obtained from the Gene Expression Omnibus (GEO) GSE52068 dataset. The GPR135 promoter region methylation level in four normal nasopharyngeal epithelial tissues and eight NPC tissues was detected by bisulfite sequencing. GPR135 expression in NPC and normal nasopharyngeal tissue was obtained from the GEO GSE13597 dataset.The GPR135 mRNA expression levels in 13 NPC and 26 healthy control tissues were assessed with quantitative real-time PCR (qRT-PCR). The GPR135 expression level in 124 NPC tissue sections was analyzed by immunohistochemistry. The correlation between GPR135 expression and clinicopathological features was analyzed by a chi-square test. GPR135 expression in patients with NPC was evaluated by immunohistochemistry, and its influence on prognosis was assessed by Kaplan-Meier and Cox regression analyses. Results The bisulfite sequencing demonstrated that the GPR135 promoter region was highly methylated in NPC tissues. The immunohistochemistry results revealed that patients with high GPR135 expression had better overall survival (hazard ratio [HR] = 0.177, 95% confidence interval [95%CI]: 0.072–0.437, P = 0.008), disease-free survival (HR = 0.4401, 95%CI: 0.222–0.871, P = 0.034), and local recurrence-free survival (HR = 0.307, 95%CI: 0.119–0.790, P = 0.046) than those with low GPR135 expression. Conclusion GPR135 is hypermethylated in NPC, where high GPR135 expression indicates a positive prognosis. Therefore, GPR135 might be a prognostic indicator.