肺腺癌中C-met的表达与EGFR-TKIs耐药的相关性研究

发布时间：2018-11-24 19:21

【摘要】：目的:检测肺腺癌中C-met蛋白表达与基因扩增情况,探讨二者与临床病理特征的关系,并分析其与EGFR-TKIs耐药和预后的关系。方法:选取120例(80例接受EGFR-TKIs治疗,40例未接受EGFR-TKIs治疗)肺腺癌组织。1.应用免疫组织化学EnVision方法进行TTF-1、Napsin A、CK7及C-met蛋白表达检测。2.应用荧光原位杂交技术(FISH)进行C-met基因扩增状态检测。结果:1.120例肺腺癌组织中C-met蛋白高表达者21例,C-met基因扩增者13例。80例接受EGFR-TKIs治疗的患者中,46例出现靶向耐药,C-met蛋白高表达30.43%(14/46),C-met基因扩增19.57%(9/46),两者均高于接受靶向治疗而未出现耐药表现患者。2.C-met蛋白高表达与年龄、病理分级、临床分期有关(P0.05),而与性别、吸烟史、淋巴结转移无关(P0.05)。C-met基因扩增与临床分期有关(P0.05),而与年龄、性别、吸烟史、病理分级、淋巴结转移无关(P0.05)。3.耐药患者中,蛋白高表达且基因扩增者6例,统计分析表明,耐药患者中C-met蛋白高表达与基因扩增二者呈正相关(rs=0.388)。而40例未接受TKIs治疗患者中C-met蛋白高表达与基因扩增差异无统计学意义(P0.05)。4.C-met基因扩增阴性组患者3年生存率高于基因扩增阳性组,差异有统计学意义(P0.05);C-met蛋白低表达组患者3年生存率高于C-met蛋白高表达组,但差异无统计学意义(P0.05)。Cox回归分析表明,C-met基因扩增是影响预后的独立因素。结论:1.C-met在肺腺癌中处于高表达状态。2.C-met蛋白高表达与年龄、病理分级、临床分期有关。C-met基因扩增与临床分期有关。3.接受靶向治疗而出现耐药表现的肺腺癌患者中,C-met蛋白表达与基因扩增具有相关性。4.C-met基因扩增提示预后较差,可作为预后评估的一个独立因素。
[Abstract]:Objective: to investigate the relationship between C-met protein expression and gene amplification in lung adenocarcinoma and its relationship with clinicopathological features, drug resistance and prognosis of EGFR-TKIs. Methods: 120 cases of lung adenocarcinoma (80 cases treated with EGFR-TKIs and 40 cases not treated with EGFR-TKIs) were selected. 1. Immunohistochemical EnVision method was used to detect the expression of TTF-1,Napsin ACK7 and C-met protein. 2. The amplification status of C-met gene was detected by fluorescence in situ hybridization (FISH). Results: there were 21 cases of high expression of C-met protein and 13 cases of C-met gene amplification in 1.120 cases of lung adenocarcinoma. In 80 cases of patients treated with EGFR-TKIs, 46 cases showed targeted drug resistance, and the overexpression of C-met protein was 30.43% (14 / 46). The C-met gene amplification rate was 19.57% (9 / 46). The high expression of 2.C-met protein was correlated with age, pathological grade and clinical stage (P0.05), but with sex. C-met gene amplification was related to clinical stage (P0.05), but not to age, sex, smoking history, pathological grade, lymph node metastasis (P0.05). There were 6 cases of high protein expression and gene amplification in drug-resistant patients. Statistical analysis showed that the high expression of C-met protein was positively correlated with gene amplification (rs=0.388) in drug-resistant patients. However, there was no significant difference between the high expression of C-met protein and gene amplification in 40 patients without TKIs (P0.05). The 3-year survival rate of 4.C-met gene negative group was higher than that of gene amplification positive group. The difference was statistically significant (P0.05). The 3-year survival rate of patients with low expression of C-met protein was higher than that of patients with high expression of C-met protein, but the difference was not statistically significant (P0.05). Cox regression analysis showed that C-met gene amplification was an independent factor affecting prognosis. Conclusion: the expression of 1.C-met is high in lung adenocarcinoma. The high expression of 2.C-met protein is related to age, pathological grade and clinical stage. The amplification of C-met gene is related to clinical stage. The expression of C-met protein was correlated with gene amplification in lung adenocarcinoma patients with drug resistance after targeted therapy. 4.C-met gene amplification suggested poor prognosis and could be used as an independent prognostic factor.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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