Study On The Correlation Between C-met Expression And EGFR-TKIs Resistance In Lung Adenocarcinoma

Objective:The aim of the study was to obeserve C-met protein expression and gene amplification in lung adenocarcinoma,to probe into their relationship with the clinicopathological features,and to analyse their relationship between EGFR-TKIs resistance and prognosis.Methods:120 cases of lung adenocarcinoma tissues were selected(80 cases treated with EGFR-TKIs and 40 cases not treated with EGFR-TKIs).1.The expressions of TTF-1,Napsin A,CK7 and C-met protein were detected using immunohistochemistry EnVision method.2.Detection of C-met gene amplification was conducted by fluorescence in situ hybridization(FISH).Results:1.There were 21 high C-met protein expression cases and 13 C-met gene amplification cases in 120 lung adenocarcinoma patients.Of the 80 patients treated with EGFR-TKIs,46 were resistant to TKIs.C-met protein was highly expressed in 30.43% cases(14/46)and C-met gene amplification accounted for 19.57%(9/46).Both were higher than those in the patients with targeted therapy but not drug resistant.2.The high expression of C-met protein was correlated with age,pathological grade and clinical stage(P<0.05),not with sex,smoking history and lymph node metastasis(P>0.05).C-met gene amplification was related with clinical stage(P<0.05),not with age,sex,smoking history,pathological grade and lymph node metastasis(P>0.05).3.6 cases have high C-met protein expression and gene amplification in patients with drug resistance.Statistical analysis showed that high expression of C-met protein was positively correlated with gene amplification(rs=0.388).However,the difference was not statistically significant between high expression of C-met protein and gene amplification of the 40 patients not treated with TKIs(P>0.05).4.The 3-year survival rate of the negative C-met gene amplification group was higher than that of positive group,and the difference was statistically significant(P<0.05).The 3-year survival rate of patients with low C-met protein expression was higher than that of high expression group,but the difference was not statistically significant(P>0.05).Cox regression analysis suggested that C-met gene amplification was an independent prognostic factor.Conclusions:1.C-met is in a state of high expression in lung adenocarcinoma.2.The high expression of C-met protein is correlated with age,pathological grade and clinical stage,while C-met gene amplification is related to clinical stage.3.The expression of C-met protein is correlated with gene amplification in drug-resistant lung adenocarcinoma patients treated with targeted therapy.4.C-met gene amplification suggests poor prognosis,and can be used as an independent factor for prognostic evaluation.