抑癌基因脾酪氨酸激酶和人类Runt相关转录因子3基因启动子甲基化与胃癌术后复发转移的关系

Relationship between promoter methylation of Syk and Runx3 genes and postoperative recurrence and metastasis in gastric carcinoma

目的探讨抑癌基因脾酪氨酸激酶（Syk）和人类Runt相关转录因子3（Runx3）启动子甲基化与胃癌术后复发转移的关系。方法采用甲基化特异性PCR检测70例胃癌组织和癌旁胃正常组织中Syk和Runx3基因启动子甲基化状态。结果在70例胃癌组织中，Syk和Runx3基因启动子甲基化发生率分别为45．7％（32／70）和55．7％（39／70）；在癌旁胃正常组织中，Syk和Runx3基因启动子甲基化发生率分别为0（0／70）和7．1％（5／70）。胃癌组织中Syk和Runx3基因启动子甲基化发生率明显高于癌旁胃正常组织（均P〈0．001）。Syk、Runx3基因启动子甲基化与肿瘤的分化程度、浸润深度、淋巴结转移和病理分期有关（均P〈0．05）。32例Syk基因启动子甲基化患者中，有21例患者术后发生复发转移，复发转移发生率为65．6％（21／32）；38例Syk基因启动子非甲基化患者中，仅有7例患者术后发生复发转移，复发转移发生率为18．4％（7／38），差异有统计学意义（P〈0．001）。39例Runx3基因启动子甲基化患者中，有24例患者术后发生复发转移，复发转移发生率为61．5％（24／39）；31例Runx3基因启动子非甲基化患者中，仅有4例患者术后发生复发转移，复发转移发生率为12．9％（4／31），差异有统计学意义（P〈0．001）。结论Syk和Runx3基因启动子甲基化与胃癌术后复发转移密切相关。Syk和Runx3基因启动子甲基化的联合检测有助于胃癌术后复发转移的早期诊断和预后评估。

Objeetive To investigate the relationship between aberrant methylation of Syk and Runx3 genes and recurrence and metastasis after resection of gastric cancer. Methods Applying methylation-specific polymerase chain reaction technique, promoter methylation of Syk and Runx3 genes in the tumor tissues and adjacent normal tissues of gastric cancer patients were detected to investigate the relationship between methylation status of the promoter region of Syk and Runx3 genes and postoperative recurrence and metastasis. Results In the 70 cases of gastric cancer, the frequencies of promoter methylation of Syk and Runx3 genes were 45.7% （32/70） and 55.7% （39/70） in gastric cancer, and 0 （0/70） and 7.1% （5/70） , respectively, in the adjacent normal tissues. The rates of promoter methylation of Syk and Runx3 genes in the gastric cancers were significantly higher than that in the adjacent normal tissues （P 〈 0. 001 for all）. The promoter methylation of Syk and Runx3 genes was significantly correlated with the degree of tumor differentiation, depth of invasion, lymph node metastasis and pathological staging （P 〈 0. 05 for all）. The frequency of postoperative recurrence and metastasis in 32 patients with Syk promoter methylation was 65.6% （21/32） and that in 38 cases with Syk promoter unmethylation was 18.4% （7/38）, showing a significant difference between the two subgroups （χ^2 = 16.13, P 〈0. 001 ）. Therate of postoperative recurrence and metastasis in 39 patients with Runx3 promoter methylation was 61.5% （24/39） and that in 31 patients with Runx3 promoter unmethylation was 12.9% （4/31, P 〈 0, 001 ）. Conclusions The methylation of Syk and Runx3 promoters plays an important role in postoperative recurrence and metastasis of gastric cancer. Combined detection of promoter methylation of Syk and Runx3 genes is helpful for early diagnosis and evaluation of prognosis of gastric cancer.