The Detection Of Egfr And Emt, And Its Relationship With The Efficacy Of Egfr-Tkis As The Second Line Treatment In Advanced Nsclc

On the phenomenon that efficacy and survival advantages are not very well reflected, and NSCLC patients were indiscriminately given EGFR-TKIs as the second line treatment, we have detected EGFR gene mutation EGFR protein and the status of EMT, to analyse its expression and significance (sex、age、smoking history and tissue typing), and its relationship with the efficacy of EGFR-TKIs as the second line treatment, in order to search possible predictor of EGFR-TKIs as the second line treatment. It’s a preliminary study about what are ways preferably chosen for advanced NSCLC patients in EGFR-TKIs as the second line treatment.It was collecting the clinic and pathologic data of78advanced NSCLC patients who were treated with EGFR-TKIs in Air Force General Hospital. These patients had adopted2-4periods chemotherapy in the past treatment, and took orally EGFR-TKIs more than one month. The NSCLC pathological specimens derived from puncture and biopsy. Mutation of EGFR gene from tumor tissue was detected by polymerase chain reaction (PCR) and direct sequencing. The characteristic protein (E-cadherin、Vimentin) of EMT and the expression of EGFR were detected by immunohistochemistry. E-cadherin positive and Vimentin negative stand for EMT(-), be epithelial type; Vimentin positive and E-cadherin negative stand for EMT(+), be interstitial type. Select the known positive expression of NSCLC as positive control specimen and PBS replace first Ab as negative control. Efficacy evaluation of solid tumor were according to the CT image database data, and solid tumor response evaluation criteria in solid tumor(RECIST) to calculate the objective response rates(ORR) and disease control rates(DCR); The overall survival(OS) rate were calculated by the phone and outpatient follow-up. Statistical analysis using SPSS17.0software system, P<0.05stand for having a statistical significance, count material by chi-square test, the relationship between protein was analysed by the spearman rank correlation analysis, single factor survival analysis using Kaplan-Meier analysis, multi-factor survival analysis using COX regression analysis.In78advanced NSCLC patients, EGFR gene mutation rate was24.4%,16normal lung tissue, and the EGFR sequences were wild type, the positive expression rate of EGFR and E-cadherin, Vimentin were61.5%、43.6%and56.4%, the expression of E-cadherin and Vimentin have good consistency. In normal lung tissue, the EGFR protein and E-cadherin protein are positive, Vimentin protein is negative. The EGFR gene mutation rate in female and adenocarcinoma was higher than male and squamous carcinoma(P<0.05), the positive expression rate of EGFR in adenocarcinoma was higher than squamous carcinoma(P<0.05), the occurrence rate of EMT in male was higher than female(P<0.05), EGFR expressing has no relation with gene mutation, epithelial type patients in EGFR mutation type was higher than EGFR wild type(P<0.05), the expression of EGFR was correlate with the occurrence of EMT(r=0.252, P<0.05). ORR and DCR in EGFR mutation type (36.8%、60.2%)was higher than EGFR wild type(10.2%、15.5%)(P<0.05), ORR and DCR in epithelial type(33.9%、57.7%) was higher than interstitial type(9.5%、21.3%)(P<0.05). The median survival times of EGFR mutation type group and EGFR wild type group were13months and7months(P<0.05), epithelial type group and interstitial type group were15months and5months(P<0.05), EGFR positive group and negative group were9months and10months(P>0.05). Age and sex, tissue typing, smoking, EMT, EGFR protein and mutation bring into COX regression analysis reveal the risk of death in epithelial type group was4.850times higher than interstitial type group (95%CI:2.283-10.301).Through this experiment, we come to the following conclusions, EGFR mutation is still one of the forecast efficacy factors in EGFR-TKIs second line treatment. EGFR expressing has no relation with gene mutation, that is the expression of EGFR can’t reflect EGFR mutation, EGFR overexpression has no relationship with the efficacy of EGFR-TKIs as the second line treatment in advanced NSCLC. EMT may be one of the predictor in EGFR-TKIs second line treatment, EMT is one influence factor of overall survival. EGFR protein and EMT generation have synergy, so detecting EMT combine with EGFR protein is usefull for judging the degree of malignant tumor, for clinical treatment and prognosis to provide more effective basis. We discovered that EGFR mutation patients weren’t easily influenced by EMT, but EGFR wild type patients were easy to have EMT, so detecting EMT combine with EGFR mutation is usefull for choosing advantage people in EGFR-TKIs second line treatment.