Telomerase reverse transcriptase methylation predicts lymph node metastasis and prognosis in patients with gastric cancer.
Telomerase reverse transcriptase methylation predicts lymph node metastasis and prognosis in patients with gastric cancer.
复制标题
端粒酶逆转录酶甲基化预测胃癌患者淋巴结转移和预后
DOI：
10.2147/ott.s97899
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发表时间：
2016
影响因子：
4
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Wu Y;Li G;He D;Yang F;He G;He L;Zhang H;Deng Y;Fan M;Shen L;Zhou D;Zhang Z
目的端粒酶活性与细胞永生化有关，在大多数人类肿瘤中存在，而在正常组织中不存在。端粒酶逆转录酶（telomerase reverse transcriptase，TERT）是一种催化端粒酶活性的亚单位，其活性与肿瘤中端粒酶活性密切相关.本研究的目的是探讨端粒酶启动子甲基化及其对胃癌预后的影响。患者与方法采用高度敏感的Sequenom Epityper分析法，对116例胃癌患者的肿瘤及相应正常组织进行了端粒酶启动子甲基化分析。采用实时定量聚合酶链反应检测胃癌组织中端粒酶逆转录酶的表达。结果胃癌组织中端粒酶启动子甲基化水平显著高于癌旁正常组织（P=0.002）。TERT启动子甲基化与高T分期（P=0.024）、晚期N分期（P=0.006）和淋巴血管/神经浸润（P=0.035）相关，与年龄、性别和组织学分级无关。一元线性回归分析显示，TERTmRNA与TERTmRNA甲基化呈正相关（R2=0.562，P=0.001）。胃癌组织中TERTmRNA的高表达与TERTmRNA启动子的高甲基化有关（P=0.005）。单因素分析显示N分期（P=0.002）和TERT启动子甲基化（P=0.004）是总生存期的预测因素。此外，多因素分析证实N分期（P=0.013）和TERT启动子甲基化（P=0.031）是总生存期的独立预后指标。结论胃癌组织中TERT基因启动子区甲基化可能与胃癌的胃壁浸润、淋巴结转移、淋巴管/神经浸润及预后不良有关。伴有TERT基因启动子高甲基化的胃癌患者可进行密切随访。
Purpose Telomerase activity is associated with cellular immortalization and is present in most human tumors but absent in normal tissues. The activity of telomerase reverse transcriptase (TERT), a catalytic telomerase subunit, correlates with telomerase activity in tumors. The objective of this study was to investigate TERT promoter methylation and its prognostic impact in gastric cancer (GC). Patients and methods The analysis of TERT promoter methylation was performed in tumors and corresponding normal tissues of 116 patients with GC using a highly sensitive Sequenom Epityper assay. The expression of TERT in GC tissues was measured by quantitative real-time polymerase chain reaction. Results The levels of TERT promoter methylation in GC samples were significantly higher than in normal adjacent tissues (P=0.002). Hypermethylation of TERT promoter was associated with high T-stage (P=0.024), late N-stage (P=0.006), and lymphovascular/neural invasion (P=0.035), without correlation with age, sex, or histological grade. Simple linear regression analysis showed that TERT mRNA correlated positively with TERT methylation (R2=0.562, P=0.001). Also, higher TERT mRNA expression was related to hypermethylation of TERT promoter in GC samples (P=0.005). Univariate analysis demonstrated that N-stage (P=0.002) and TERT promoter methylation (P=0.004) were predictive of overall survival. Furthermore, multivariate analysis confirmed that N-stage (P=0.013) and TERT promoter methylation (P=0.031) were independent prognostic indicators for overall survival. Conclusion Our data suggested that hypermethylation of TERT promoter may contribute to gastric wall invasion, lymph node metastasis, lymphovascular/neural invasion, and poor prognosis in GC. GC patients with hypermethylation of TERT promoter could be eligible for close follow-up.