【摘要】：目的:檢測(cè)肺腺癌中C-met蛋白表達(dá)與基因擴(kuò)增情況,探討二者與臨床病理特征的關(guān)系,并分析其與EGFR-TKIs耐藥和預(yù)后的關(guān)系。方法:選取120例(80例接受EGFR-TKIs治療,40例未接受EGFR-TKIs治療)肺腺癌組織。1.應(yīng)用免疫組織化學(xué)EnVision方法進(jìn)行TTF-1、Napsin A、CK7及C-met蛋白表達(dá)檢測(cè)。2.應(yīng)用熒光原位雜交技術(shù)(FISH)進(jìn)行C-met基因擴(kuò)增狀態(tài)檢測(cè)。結(jié)果:1.120例肺腺癌組織中C-met蛋白高表達(dá)者21例,C-met基因擴(kuò)增者13例。80例接受EGFR-TKIs治療的患者中,46例出現(xiàn)靶向耐藥,C-met蛋白高表達(dá)30.43%(14/46),C-met基因擴(kuò)增19.57%(9/46),兩者均高于接受靶向治療而未出現(xiàn)耐藥表現(xiàn)患者。2.C-met蛋白高表達(dá)與年齡、病理分級(jí)、臨床分期有關(guān)(P0.05),而與性別、吸煙史、淋巴結(jié)轉(zhuǎn)移無(wú)關(guān)(P0.05)。C-met基因擴(kuò)增與臨床分期有關(guān)(P0.05),而與年齡、性別、吸煙史、病理分級(jí)、淋巴結(jié)轉(zhuǎn)移無(wú)關(guān)(P0.05)。3.耐藥患者中,蛋白高表達(dá)且基因擴(kuò)增者6例,統(tǒng)計(jì)分析表明,耐藥患者中C-met蛋白高表達(dá)與基因擴(kuò)增二者呈正相關(guān)(rs=0.388)。而40例未接受TKIs治療患者中C-met蛋白高表達(dá)與基因擴(kuò)增差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。4.C-met基因擴(kuò)增陰性組患者3年生存率高于基因擴(kuò)增陽(yáng)性組,差異有統(tǒng)計(jì)學(xué)意義(P0.05);C-met蛋白低表達(dá)組患者3年生存率高于C-met蛋白高表達(dá)組,但差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。Cox回歸分析表明,C-met基因擴(kuò)增是影響預(yù)后的獨(dú)立因素。結(jié)論:1.C-met在肺腺癌中處于高表達(dá)狀態(tài)。2.C-met蛋白高表達(dá)與年齡、病理分級(jí)、臨床分期有關(guān)。C-met基因擴(kuò)增與臨床分期有關(guān)。3.接受靶向治療而出現(xiàn)耐藥表現(xiàn)的肺腺癌患者中,C-met蛋白表達(dá)與基因擴(kuò)增具有相關(guān)性。4.C-met基因擴(kuò)增提示預(yù)后較差,可作為預(yù)后評(píng)估的一個(gè)獨(dú)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.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R734.2

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