Medical Genetics Center, Department of Genetics, School of Medicine, Ningbo University, Ningbo, Zhejiang, PR China.
Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, PR China.
Future Oncol. 2019 Apr;15(11):1279-1289. doi: 10.2217/fon-2018-0674. Epub 2019 Mar 29.
This study investigated the association between GPX3 methylation and gastric cancer (GC), and explored its prognostic value in patients undergoing radical gastrectomy.
MATERIALS & METHODS: The methylation levels of tumor and paracancerous tissues were detected by quantitative methylation-specific PCR method.
GPX3 was hypermethylated in GC (p = 4E-4), and was specific for patients with lymphatic metastasis (+), tumor invasion depth >3 cm and patients with poor differentiation. Additionally, GPX3 hypermethylation predicts a tumor recurrence in patients aged >60 (p = 0.019). Data from The Cancer Genome Atlas (TCGA) further confirmed GPX3 hypermethylation (cg21504918: -0.08 vs -0.25, p = 0.001). Additionally, TCGA showed an inverse correlation between GPX3 methylation and expression (p = 7E-18, r = -0.427). Data analysis of Gene Expression Omnibus (GEO) database showed that 5-aza-2'-deoxycytidine demethylating agent increased GPX3 expression (fold-change >2.19, p = 0.001).
Our results indicated GPX3 hypermethylation in GC, and predicted a shorter tumor recurrence time in patients aged >60.
本研究旨在探讨谷胱甘肽过氧化物酶 3(GPX3)甲基化与胃癌(GC)的关系,并探讨其在接受根治性胃切除术患者中的预后价值。
采用定量甲基化特异性 PCR 方法检测肿瘤和癌旁组织的甲基化水平。
GC 中 GPX3 呈高甲基化(p=4E-4),并且对有淋巴转移(+)、肿瘤浸润深度>3cm 和分化差的患者具有特异性。此外,GPX3 高甲基化预示着>60 岁患者的肿瘤复发(p=0.019)。来自癌症基因组图谱(TCGA)的数据进一步证实了 GPX3 高甲基化(cg21504918:-0.08 与-0.25,p=0.001)。此外,TCGA 显示 GPX3 甲基化与表达呈负相关(p=7E-18,r=-0.427)。基因表达综合数据库(GEO)的数据分析显示,5-氮杂-2'-脱氧胞苷去甲基化剂增加了 GPX3 的表达(倍数变化>2.19,p=0.001)。
我们的研究结果表明 GC 中存在 GPX3 高甲基化,并预测>60 岁患者的肿瘤复发时间更短。