胃癌组织及相关淋巴结中端粒酶逆转录酶基因启动子区域甲基化检测的临床意义

Clinical Effect of DNA Methylation Promoter Region of the Human Telomerase Reverse Transcriptase Gene in Gastric Cancer Tissue and Lymph Node

[目的]检测胃癌患者肿瘤组织及其相应的癌旁组织和淋巴结组织中端粒酶逆转录酶(hTERT)基因启动子区域甲基化状态,并探讨其甲基化状态的改变与临床病理特征的关系。[方法]运用甲基化特异性PCR(MSP)方法,检测52例手术切除胃癌组织、癌旁组织及相关淋巴结中hTERT基因启动子区域甲基化状态,以同一标本正常组织作为阴性对照。[结果]正常胃黏膜组织未检测出hTERT表达,胃癌组织及癌旁组织、转移淋巴结中均检测出hTERT表达。转移淋巴结、胃癌组织中hTERT基因的甲基化阳性率分别为81.6%(31/38)、71.1%(37/52),明显高于癌旁组织的29.5%(13/52)(P<0.01)。胃癌组织hTERT基因甲基化阳性率与胃癌的临床分期、组织分化程度、肿瘤大小有相关性(P<0.05)。癌旁组织hTERT基因甲基化阳性率和胃癌的临床分期、肿瘤大小、组织分化程度、淋巴结转移具有相关性(P<0.05)。转移淋巴结hTERT基因甲基化阳性率则与临床及病理特征无关。[结论]胃癌组织及转移淋巴结中存在hTERT基因启动子区域的异常甲基化调控,可能参与了胃癌的发生与发展。

[Purposel To detect level of human telomerase reverse transcriptase （hTERT） promoter methylation in gastric cancer and lymph nodes and to examine the association of methylation level with clinical and pathological characteristics. [MethodsJ Methylation specific polymerase chain reac- tion （MSP） was introduced to detect hTERT promoter methylation in tumor tissue, lymph node and tumor adjacent tissues from 52 patients with gastric cancer and in normal gastric tissues from same patients. [Results] Promoter methylation of hTERT gene were found in 81.6%（31/38） of metastastic lymph node and 71.1%（37/52） of the gastric carcinoma tissues, 29.5%（13/52） of carcinoma adjacent tissues, but 0/52 of normal control. Furthermore, methylation levels in both metastastic lymph node and the gastric carcinoma tissues was significantly higher than that in carcinoma adjacent tissues （P〈 0.01）. The positive rate of hTERT gene methylation was significantly related to clinical stage, tissue differentiation and tumor size of （P〈0.05）.The positive rate of hTERT gene methylation in carcinoma adjacent tissues was significantly related to clinical stage,lymph node metastasis, tissue differentia- tion of carcinoma and tumor size （P〈0.05）. However, methylation in metastastic lymph node was un- related to the clinical and pathological characteristics. [Conclusion] Aberrant methylation of the pro- moter of hTERT gene in gastric carcinoma tissues and carcinoma adjacent tissues is common. It indi- cates that methvlation of hTERT gene takes Dart in the development of zastric cancer.