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目的研究胃癌Runx3基因甲基化和幽门螺杆菌(H.pylori)感染、临床病理特征及患者生存的关系。方法筛选我院肿瘤外科2004年6月至2005年12月86例病理确诊的原发性胃癌患者,男性52例,女性34例,平均年龄52(28～78)岁。20例正常对照选自同期我院消化内科门诊。用甲基化特异性PCR(MSP)法检测胃癌组织、癌旁组织及正常对照组织中Runx3基因甲基化状况;用快速尿素酶诊断法和Warthin-Starry染色法检测胃癌患者及对照组H.pylori感染状况;用Kaplan-Meier限乘法计算生存率;用Cox比例风险回归模型进行多因素生存分析。结果①胃癌组织Runx3甲基化率(65.1%,56/86)明显高于相应癌旁组织(8.1%,7/86)和正常对照组织(0/20)(P<0.01)。②Runx3甲基化与组织分化(P=0.017)、浸润深度(P=0.004)及淋巴结转移(P=0.001)等显著相关。③H.pylori感染的胃癌组织Runx3甲基化率较未感染的胃癌组织高(P=0.003)。④Kaplan-Meier生存曲线经Log-rank检验发现Runx3甲基化与生存相关(P<0.01)。⑤多因素生存分析显示浸润深度、Runx3甲基化是胃癌的独立预后因素(P<0.05)。结论胃癌Runx3甲基化与肿瘤进展和转移有关,H.pylori感染增加Runx3甲基化,Runx3甲基化是胃癌的独立预后因素。
Objective To investigate the relationship between Runx3 gene methylation and H. pylori infection in gastric cancer, clinicopathological features and survival. Methods Totally 86 patients with pathologically diagnosed primary gastric cancer from June 2004 to December 2005 in our department were enrolled. There were 52 males and 34 females with an average age of 52 to 28 years old. 20 cases of normal control selected from the same period our hospital digestive medicine clinic. The methylation status of Runx3 gene was detected by methylation-specific PCR (MSP) in gastric cancer tissue, paracancerous tissues and normal control tissues. Gastric cancer patients and control group H were detected by rapid urease assay and Warthin-Starry staining. pylori infection; Survival rate was calculated by Kaplan-Meier limit multiplication; Cox proportional hazards regression model was used for multivariate survival analysis. Results ① The rates of Runx3 methylation (65.1%, 56/86) in gastric cancer tissues were significantly higher than those in paracancerous tissues (8.1%, 7/86) and normal controls (0/20) (P <0.01). ②Runx3 methylation was significantly associated with histological differentiation (P = 0.017), depth of invasion (P = 0.004) and lymph node metastasis (P = 0.001). The methylation rate of Runx3 in H.pylori-infected gastric cancer tissues was higher than that in non-infected gastric cancer tissues (P = 0.003). ④Kaplan-Meier survival curve Log-rank test found Runx3 methylation and survival (P <0.01). ⑤Multivariate survival analysis showed that depth of invasion, Runx3 methylation was an independent prognostic factor for gastric cancer (P <0.05). Conclusion Runx3 methylation in gastric cancer is associated with tumor progression and metastasis. Runx3 methylation is up-regulated in H.pylori infection, which is an independent prognostic factor for gastric cancer.