Heterogeneous Expression Of ZNF139, Survivin And Bcl-2in Gastric Carcinoma And Metastatic Lymph Nodes

Objective: Gastric carcinoma is one of the most common malignanttumors, and its incidence is the highest in malignant digestive tumors. Themortality rate of gastric carcinoma is high and the5-year overall survival ofadvanced gastric cancer is lower than30%. Owing to lacking of specificclinical symptoms and signs in the early stage of gastric carcinoma, most casesare diagnosed in advanced stage, and some of them with distant metastasis,leading to some patients lost the optimal timing of surgery. Modern oncologyconsiders that the occurrence and development of malignant tumors are notonly correlated with fast cell proliferation, but also with the reduction in thenumber of apoptotic cells. Cell apoptosis is an initiative process of cell deathwhich is regulated by the genes, it plays an important role in the process ofgrowth in multicellular organisms, and the process must be precise controlled.The defects of apoptosis signaling pathways are common in malignant tumors,which prompt that the inhibition of apoptosis may promote the occurrence anddevelopment of tumors. However, the regulatory mechanism of tumorigenesis,development, proliferation and apoptosis in gastric carcinoma are unclear yet.It is known that many transcription factors and inhibitor of apoptosis proteinsare related to cell apoptosis. Survivin belongs to the inhibitor of apoptosisprotein family, it could confront induction of apoptosis in G2/M phase of thecell division cycle, the excessive expression of survivin in cancer can promotemalignant cells to proliferate abnormally, so the positive expression ofsurvivin is a sign of poor prognosis in malignant tumors. Besides, bcl-2familyplays an important role in the process of cell apoptosis, and includes a set ofrelated proteins. Bcl-2can prevent the occurrence of apoptosis and prolongcell survival, so it is called cell longevity gene, the expression of Bcl-2canincrease the resistance to apoptosis factors, then impel tumor to occur and develop, and also increases the invasion ability of cancer. Recently the role ofzinc finger proteins in tumor is widely concerned. The Krüppel-type ZNFgene family is one of the largest gene families of zinc finger transcriptionalfactors in the human genome. Studies have indicated that the members of theKRAB-ZNF family can regulate the transcription and translation of relativegenes and they are involved in tumorigenesis. ZNF139gene belongs to theKrüppel-type ZNF gene family. Prophase research found that the expressionof ZNF139protein is high in gastric carcinoma cell, as transcriptional factor,so it may be not only involved in the occurrence and development of gastriccarcinoma, but also the invasion and metastasis of gastric cancer cells. Thisstudy includes35cases of advanced patients with gastric cancer tissue andmetastatic lymph nodes, TdT-mediated dUTP Nick-End Labeling (TUNEL)was used to detect cell apoptosis of gastric cancer cells in gastric carcinomaand metastatic lymph nodes. And reverse transcription polymerase chainreaction (RT-PCR) was performed to evaluate the mRNA expression ofZNF139, Survivin and Bcl-2in gastric carcinoma and correspondingmetastatic lymph nodes to investigate the relationships between theirexpressions. This study may explore the relationship between ZNF139andapoptosis of gastric carcinoma, and analyzes the role of ZNF139to gastriccancer cell apoptosis in gastric carcinoma metastasis process, providing theevidence for transfer mechanism of gastric carcinoma from the angle ofapoptosis.Methods: The advanced specimens of35cases with gastric carcinomawere collected, including35cases of gastric carcinoma tissue and thecorresponding metastatic lymph nodes. TUNEL method was used to detectcell apoptosis of gastric cancer cells in gastric carcinoma and metastatic lymphnodes, and RT-PCR was performed to evaluate the mRNA expression ofZNF139, Survivin and Bcl-2in gastric carcinoma and metastatic lymph nodes,investigate the relationships between their expressions and the role of their ingastric carcinoma. SPSS13.0software was adopted to carry out the dataprocessing and analyses, the comparison of the measurement data by paired-samples t-test, conducting correlation analysis of the double variableand calculating Pearson correlative coefficient, and significance was assessedin all experiments as a probability value of P<0.05.Results:1Comparison of the apoptosis index (AI) of tumor cell between gastriccarcinoma and metastatic lymph nodes:The apoptosis index of gastric carcinoma was higher than that inmetastatic lymph nodes (10.769±4.669vs8.7±3.041, t=2.151, P=0.039).2The correlation between the expression of ZNF139, Survivin, Bcl-2andAI in gastric carcinoma and metastatic lymph nodes:The correlation between the expression of ZNF139and apoptosis indexin gastric carcinoma wasn’t obvious (r=-0.035, P=0.842). There was anegative correlation between the expression of Survivin and apoptosis index ingastric carcinoma (r=-0.517, P=0.001). The correlation between theexpression of Bcl-2and apoptosis index in gastric carcinoma wasn’t obvious(r=0.029, P=0.867). There was a negative correlation between ZNF139andapoptosis index in metastatic lymph nodes (r=-0.346, P=0.042). There was anegative correlation between Survivin and apoptosis index in metastatic lymphnodes (r=-0.467, P=0.005). Besides, There was a negative correlation betweenBcl-2and apoptosis index in metastatic lymph nodes (r=-0.511, P=0.002).3Comparison between the expression levels of ZNF139, Survivin andBcl-2in gastric carcinoma and metastatic lymph nodes and correlation:The mRNA expression of ZNF139in metastatic lymph nodes was higherthan that in gastric carcinoma (0.618±0.346vs0.334±0.232, t=-4.546,P=0.000), but there wasn’t an obvious correlation (r=0.228, P=0.187). ThemRNA expression of Survivin and Bcl-2in metastatic lymph nodes werehigher than that in gastric carcinoma (0.693±0.304vs0.492±0.325, t=-2.667,P=0.012;0.770±0.430vs0.626±0.398, t=-3.158, P=0.003, respectively).There was a positive correlation of Bcl-2between gastric carcinoma andmetastatic lymph nodes (r=0.79, P=0.000), the correlation of Bcl-2betweengastric carcinoma and metastatic lymph nodes wasn’t obvious (r=-0.004, P=0.98).4The correlation between the expression of ZNF139, Survivin and Bcl-2in gastric carcinoma and metastatic lymph nodes:Pearson correlation analysis shows that there was a positive correlationbetween the mRNA expression of ZNF139and Bcl-2in gastric carcinoma(r=0.482, P=0.003). And there wasn’t an obvious correlation between themRNA expression of ZNF139and Survivin in gastric carcinoma (r=-0.093,P=0.596). Besides, There wasn’t an obvious correlation between the mRNAexpression of Survivin and Bcl-2in gastric carcinoma (r=-0.067, P=0.701).There was a positive correlation between ZNF139and Survivin or Bcl-2in metastatic lymph nodes in mRNA level (r=0.436, P=0.009; r=0.452,P=0.006, respectively). Besides, There was a positive correlation between themRNA expression of Survivin and Bcl-2in metastatic lymph nodes (r=0.465,P=0.005).Conclusions:1The apoptosis index of metastatic lymph nodes is inferior to that ingastric carcinoma, prompting that apoptosis resistance ability of gastriccarcinoma cell has enhanced in the process of metastasis.2The expression of ZNF139, Survivin and Bcl-2in metastatic lymphnodes is higher than that in gastric carcinoma, implying that they haveheterogeneity between gastric carcinoma and metastatic lymph nodes. It pointsout that ZNF139maybe involved in tumorigenesis of gastric carcinoma, andinvasion and metastasis of cancer cells.3Correlation analysis shows that there is a positive correlation betweenthe expression of ZNF139and Bcl-2in gastric carcinoma, there isn’t anobvious correlation between the expression of ZNF139and Survivin in gastriccarcinoma. It points out that ZNF139maybe involved in the development ofgastric carcinoma by regulating Bcl-2. However, there is a positive correlationbetween ZNF139and Survivin or Bcl-2in metastatic lymph nodes, whichindicates that ZNF139maybe regulate different genes in gastric carcinomaand metastatic lymph nodes. Besides, it also indicates that the regulative pathways of apoptosis may change continuously in the process of invasion andmetastasis of gastric cancer cells, while ZNF139have changed in this process.