胃癌组织中NLRC5表达的意义及其影响胃癌侵袭转移的可能机制

发布时间：2018-06-13 20:01

  本文选题：胃癌 + NLRC　； 参考：《安徽医科大学学报》2017年10期

【摘要】：目的观察核苷酸结合结构域受体家族含CARD结构域-5(NLRC5)、β-catenin在胃癌组织中的表达情况。分析NLRC5与胃癌临床病理特征及预后的关系。并初步探讨NLRC5与Wnt/β-catenin信号通路间的关系。方法收集根治性胃癌切除术患者石蜡标本93例,免疫组化检测胃癌组织中NLRC5和β-catenin的表达情况;分析NLRC5的表达与胃癌临床病理特征的关系。采用胃癌细胞株MKN-45和MGC-803分别转染p EGFP-C2-NLRC5重组质粒,qRT-PCR法和Western blot法验证NLRC5转染效率。采用MTT细胞增殖和细胞划痕实验对NLRC5进行功能分析,观察体外实验中NLRC5表达变化对胃癌细胞的生物学行为的影响,采用Western blot法检测Wnt/β-catenin信号通路相关蛋白的变化。结果 NLRC5在93例胃癌标本中阳性表达67例(72.04%),阴性表达26例(27.96%)。NLCR5的表达情况与胃癌的TNM分期、淋巴结转移和复发情况密切相关。Kaplan-merier生存分析结果显示NLCR5阴性表达的患者预后好于阳性表达患者(P0.05)。93例胃癌标本中β-catenin阳性表达63例(67.74%),阴性表达30例(32.26%)。Cox多因素回归分析显示,NLRC5和β-catenin的阳性表达、低TNM分期、淋巴结转移是影响胃癌患者预后的独立危险因素。胃癌细胞在过表达NLRC5后,MTT细胞增殖和划痕实验结果显示,细胞的增殖和迁移能力显著增强(P0.05,P0.01),Western blot实验结果显示,Wnt/β-catenin信号通路中关键蛋白β-catenin和下游关键靶蛋白C-myc、金属基质蛋白酶-7的表达水平明显提高。结论 NLRC5广泛表达于胃癌组织中,其表达与胃癌的TNM分期和淋巴结转移密切相关。Kaplan-merier生存分析显示:NLRC5高表达是影响胃癌预后的危险因素。Cox多因素回归分析显示:NLRC5高表达是影响胃癌预后的独立危险因素。NLRC5与β-catenin的表达呈正相关性,NLRC5的表达变化影响胃癌细胞的生物学行为和Wnt/β-catenin信号通路的关键蛋白的表达。提示NLRC5可能通过调控Wnt/β-catenin信号通路影响胃癌的浸润和转移。
[Abstract]:Objective to investigate the expression of nucleotide binding domain receptor family (NLRC5, 尾 -catenin) in gastric carcinoma. To analyze the relationship between NLRC 5 and clinicopathological features and prognosis of gastric cancer. The relationship between NLRC5 and Wnt / 尾 -catenin signaling pathway was studied. Methods the expression of NLRC5 and 尾 -catenin was detected by immunohistochemistry in 93 paraffin specimens of patients with radical gastrectomy, and the relationship between the expression of NLRC5 and clinicopathological features of gastric cancer was analyzed. The transfection efficiency of pEGFP-C2-NLRC5 was verified by pEGFP-C2-NLRC5 recombinant plasmid pEGFP-C2-NLRC5 transfected with MKN-45 and MGC-803 by Western blot and RT-PCR respectively. The function of NLRC5 was analyzed by MTT cell proliferation and scratch assay. The effect of NLRC5 expression on the biological behavior of gastric cancer cells was observed in vitro. The changes of Wnt- 尾 -catenin signaling pathway related proteins were detected by Western blot assay. Results the positive expression of NLRC5 in 93 cases of gastric cancer was 72.04%, and the negative expression of NLRC5 was 27.96% in 26 cases, and the TNM stage of gastric cancer. The results of Kaplan-merier survival analysis showed that the prognosis of patients with negative expression of NLCR5 was better than that of patients with positive expression of P0.05. 93 cases of gastric cancer. 63 cases of positive expression of 尾 -catenin and 30 cases of negative expression of 尾 -catenin were analyzed by multivariate regression analysis. The positive expression of NLRC5 and 尾 -catenin, Low TNM staging and lymph node metastasis are independent risk factors for prognosis of gastric cancer patients. After overexpression of NLRC5 in gastric cancer cells, MTT cell proliferation and scratch test showed that, The cell proliferation and migration were significantly enhanced by P0.05P0.01P0.01Western blot. The results showed that the expression of 尾 -catenin, C-mycand metalloproteinase-7 in Wnt/ 尾 -catenin signaling pathway was significantly increased. Conclusion NLRC5 is widely expressed in gastric carcinoma. Kaplan-merier survival analysis showed that the high expression of 1% NLRC5 was a risk factor for the prognosis of gastric cancer. Cox multivariate regression analysis showed that the high expression of 1% NLRC5 was an independent risk factor for the prognosis of gastric cancer. The expression of NLRC5 was positively correlated with the expression of 尾 -catenin. The expression of NLRC5 affected the biological behavior of gastric cancer cells and the expression of key proteins in Wnt- 尾 -catenin signaling pathway. These results suggest that NLRC5 may influence the invasion and metastasis of gastric cancer by regulating Wnt- 尾 -catenin signaling pathway.
【作者单位】： 安徽医科大学基础医学院病理学教研室;安徽医科大学第一附属医院普外科;
【基金】：国家自然科学基金(编号:81572305) 安徽省自然科学基金(编号:KJ2017A204)
【分类号】：R735.2
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本文编号：2015238