胃癌组织中TIMP-3基因甲基化水平及临床意义研究

TIMP-3 promoter methylation in gastric cancer and its clinical significance

目的探讨胃癌患者癌组织中组织金属蛋白酶抑制因子-3（TIMP-3）基因启动子CpG岛甲基化与胃癌侵袭转移能力及预后的相关性。方法运用甲基化特异性实时荧光定量聚合酶链反应（qMSP）技术检测92例胃癌患者癌组织、癌旁组织和40例正常人胃组织、48例胃炎患者胃组织中TIMP-3基因启动子CpG岛甲基化状态，分析TIMP-3基因异常甲基化与胃癌患者临床病理特征及预后之间的关系，．结果92例胃癌患者癌组织中，58例（63．0％）检测到TIMP-3基因甲基化，配对的癌旁组织中只有4例（414％）存在TIMP-3基因甲基化，正常人胃组织和胃炎组织中均没有TIMP-3基因甲基化。TIMP-3基因甲基化与肿瘤大小、生长类型、分化程度、静脉侵犯、浸润深度、淋巴结转移和临床分期问均存在相关性（均P〈005），而与患者性别、年龄、Hp感染状况以及肿瘤着生部位等无关（均P〉0．05）。生存分析表明TIMP-3基因非甲基化胃癌患者具有独立的生存优势（P〈0．01）。结论胃癌患者TIMP-3基因甲基化增强肿瘤的侵袭能力，甲基化水平和肿瘤恶性程度正相关，TIMP-3基因高甲基化提示胃癌患者不良预后。

Objective To investigate the relationship of TIMP-3 gene CpG island methylation with the invasiveness and prognosis of gastric cancer. Methods Tissue samples were collected from 92 cases of gastric cancer patients, 48 cases of gastritis and 40 healthy subjects. Methylation levels of the TIMP-3 gene promoter CpG islands were detected by methyla- tion-specific real-time polymerase chain reaction （qMSP）. The relationship of TIMP-3 gene ectopic methylation with invasiveness and prognosis for gastric cancer patients was analyzed. Results TIMP-3 gene methylation was detected in 63.0% of gastric cancer tissues and 4.4% of the paired pericancerous mucosa. TIMP-3 gene methylation was not detected in all samples from gastritis patients and normal controls. TIMP-3 gene methylation levels were correlated with tumor size, growth type, differentia- tion, lymphatic invasion, vein invasion, invasion depth, lymph node metastasis and clinical stage of gastric cancer （P〈0.05）. On the contrary, there was no correlation of TIMP-3 gene methlylation with gender, age, Hp infection status, lesion site and distant metastasis （P 〉0.05）. Survival analysis showed that patients with non-methylated TIMP-3 gene had an independent survival ad- vantage （P〈0.001）. Conclusion TIMP-3 gene methylation is correlated with the degree of malignancy and poor prognosis of gastric cancer.