胃癌原发灶和淋巴结转移灶中锌指蛋白139与肿瘤细胞凋亡和生存素及B细胞淋巴瘤/白血病-2的关系及意义研究

Relationship between ZNF139 and Tumor Cells Apoptosis,Survivin,Bcl- 2 in Gastric Cancer Primary Lesion and Metastatic Lymph Nodes and Its Significance

目的探讨胃癌原发灶和淋巴结转移灶中锌指蛋白139(ZNF139)与肿瘤细胞凋亡、生存素(Survivin)、B细胞淋巴瘤/白血病-2(Bcl-2)的关系及意义。方法选取2012年1—6月在河北医科大学第四医院外三科行手术切除的35例进展期胃癌患者为研究对象,收集患者胃癌组织及相应的淋巴结转移组织,采用DNA原位末端标记(TUNEL)法检测细胞凋亡指数(AI),反转录-聚合酶链反应(RT-PCR)检测ZNF139、Survivin、Bcl-2mRNA的相对表达水平,蛋白印迹法(Western blotting)检测ZNF139、Survivin、Bcl-2蛋白表达水平。结果胃癌原发灶AI(10.8±4.7)高于淋巴结转移灶的(8.7±3.0)(t=-2.176,P=0.039)。淋巴结转移灶ZNF139、Survivin、Bcl-2 mRNA相对表达水平均高于胃癌原发灶(P<0.05)。淋巴结转移灶ZNF139、Survivin、Bcl-2蛋白表达水平均高于胃癌原发灶(P<0.05)。胃癌原发灶Survivin mRNA相对表达水平与AI呈负相关(r=-0.517,P=0.001);淋巴结转移灶ZNF139、Survivin、Bcl-2 mRNA相对表达水平均与AI呈负相关(r=-0.346、-0.467、-0.511,P=0.042、0.005、0.002)。淋巴结转移灶Bcl-2 mRNA相对表达水平与胃癌原发灶Bcl-2 mRNA相对表达水平呈正相关(r=0.791,P<0.001)。在胃癌原发灶中,ZNF139 mRNA相对表达水平与Bcl-2 mRNA相对表达水平呈正相关(r=0.482,P=0.003)。在淋巴结转移灶中,ZNF139 mRNA相对表达水平与Survivin、Bcl-2 mRNA相对表达水平均呈正相关(r=0.436、0.452,P=0.009、0.006);Survivin mRNA相对表达水平与Bcl-2 mRNA相对表达水平呈正相关(r=0.465,P=0.005)。结论胃癌肿瘤细胞在转移过程中抗凋亡能力增强,这可能与ZNF139对部分凋亡相关基因(Survivin、Bcl-2)的调控有关,但这种调控关系在胃癌原发灶和淋巴结转移灶中并不相同。

Objective To investigate the relationship between ZNF139 and tumor cells apoptosis,Survivin,B - cell lymphoma 2（Bcl - 2）in gastric cancer primary lesions and metastatic lymph nodes and its significance. Methods 35 cases with advanced gastric cancer who underwent surgery in the Third Department of Surgery,the Fourth Hospital of Hebei Medical University from January to June 2012,were selected as study subjects,gastric cancer tissues and the corresponding metastatic lymph nodes were collected. Apoptosis index（ AI）was tested with TUNEL assay. The mRNA relative expression levels of ZNF139,Survivin and Bcl - 2 were tested by RT - PCR,the protein expression levels of ZNF139,Survivin and Bcl - 2 were tested with Western blotting assay. Results AI of gastric cancer primary lesions was significantly higher than that in metastatic lymph nodes〔（10. 8± 4. 7）vs. （8. 7 ±3. 0）,t = - 2. 176,P = 0. 039〕. The mRNA relative expression levels of ZNF139, Survivin and Bcl - 2 in metastatic lymph nodes were significantly higher than those in gastric cancer primary lesions,respectively （P ﹤ 0. 05）. The protein expression levels of ZNF139,Survivin and Bcl - 2 in metastatic lymph nodes were significantly higher than those in gastric cancer primary lesions,respectively（ P ﹤ 0. 05）. The mRNA relative expression level of Survivin was negatively correlated with AI（r = - 0. 517,P = 0. 001）;the mRNA relative expression level of ZNF139,Survivin and Bcl - 2 in metastatic lymph nodes was negatively correlated with AI,respectively（ r = - 0. 346, - 0. 467, - 0. 511;P = 0. 042, 0. 005,0. 002）. The mRNA relative expression level of Bcl - 2 in metastatic lymph nodes was positively correlated with mRNA relative expression level of Bcl - 2 in gastric cancer primary lesions（r = 0. 791,P ﹤ 0. 001）. In gastric cancer primary lesions, the mRNA relative expression level of ZNF139 was positively correlated with mRNA relative expression level of Bcl - 2（ r =0. 482,P = 0. 003）. In metastatic lymph nodes,the mRNA relative expression level of ZNF139 was positively correlated with mRNA relative expression level of Bcl - 2 and Survivin,respectively（r = 0. 436,0. 452,P = 0. 009,0. 006）;mRNA relative expression level of Survivin was positively correlated with mRNA relative expression level of Bcl - 2（r = 0. 465,P = 0. 005）. Conclusion The anti - apoptosis ability of gastric cancer cells is strengthened in the process of metastasis,which may be related to the role of ZNF139 in regulating some apoptosis related genes（Survivin,Bcl - 2）. However,the relationships of regulation are different between gastric cancer primary lesions and metastatic lymph nodes.