Correlation Between BRAF And P53 Expression And Primary Drug Resistance In The Treatment Of Advanced EGFR Mutant NSCLC

Objective: To explore the correlation between BRAF and P53 gene expression and the primary drug resistance in targeted therapy of EGFR-sensitive mutant advanced NSCLC.Methods: Collected the cases who hospitalized in the Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Bengbu Medical College from July 2016 to July 2019,and obtained biopsy tissue for the first time with ultrasound or CT guided percutaneous pulmonary puncture,ultrasound bronchoscopy(EBUS),or fiberoptic bronchoscopy The hospital’s pathology department clearly diagnosed as NSCLC and was evaluated as a mid-late stage by baseline.Genetic testing for patients with EGFR sensitive mutations(19Del,L858R)using first-generation EGFR-TKIs for first-line treatment and disease progression within 3to 6 months was included in this study(primary drug resistance),finally,32 patients were included,call for his first diagnosis of pathological wax tissue.The IHC method was used to detect the expression of BRAF and P53 protein in patients with EGFR-sensitive mutant advanced NSCLC,and to analyze the relationship between them and clinical data and the correlation between the two;follow-up record their disease progression-free time(PFS),Overall survival(OS),analysis and evaluation of its relationship with primary resistance.Results: 1.The expression of BRAF protein in EGFR mutant mid-late NSCLC is mainly located in the cytoplasm,with a positive expression rate of 40.63%(13/32).The expression of P53 protein in EGFR mutant mid-advanced NSCLC ismainly located in the nucleus,with a positive expression rate of 68.75%(22/32).2.The positive expression of P53 protein in patients with EGFR-sensitive mutant advanced NSCLC primary resistance was not related to age,gender,smoking,pathological type and distant metastasis,and the difference was not statistically significant(P>0.05).But it was related to the degree of tumor differentiation,lymph node metastasis and TNM stage,and the difference was statistically significant(P<0.05).3.The positive expression of BRAF protein in patients with EGFR-sensitive mutant advanced NSCLC primary resistance was not related to age,gender,smoking,and the difference was not statistically significant(P>0.05).But it was related to the pathological type,distant metastasis,degree of tumor differentiation,lymph node metastasis and TNM stage,and the difference was statistically significant(P<0.05).4.The incidence of primary drug resistance in BRAF-positive patients after receiving EGFR-TKIs was higher than that in BRAF-negative group,and the survival rate was lower.The difference in survival curves between the two was statistically significant(P<0.05).5.The incidence of primary drug resistance in P53-positive patients after applying EGFR-TKIs was higher than that in P53-negative group,and the survival rate was lower.The difference in survival curves was statistically significant(P<0.05).6.The incidence of primary drug resistance in the BRAF+/P53+group was significantly higher than that in the BRAF-/P53-group,PFS was shorter,overall survival was shorter,and survival rate was significantly reduced.The difference in survival curves between the two groups was statistically significant(P<0.05).Conclusion: 1.In the pathological tissue samples of patients with primary drug resistance after treatment with EGFR-TKIs in EGFR mutant mid-advanced NSCLC,the positive expression rate of BRAF was 40.63%(13/32),and the positive expression rate of P53 was 68.75%(22/32).2.The expression of BRAF and P53 genes is related to the incidence of primary resistance and overall survival after targeted therapy of EGFR mutant mid-advanced NSCLC.Patients with positive BRAF and P53 expression have a high incidence of primary resistance PFS shortened,OS shortenedsignificantly,and survival rate decreased.3.Using Fisher’s test,P=0.14,the difference was not statistically significant(P>0.05),indicating that there is no correlation between the expression of BRAF and P53 genes in patients with EGFR mutant mid-advanced NSCLC primary drug resistance.4.Detection of the expression of BRAF and P53 genes in patients with advanced EGFR mutant NSCLC has predictive value for the occurrence of primary drug resistance and overall survival after EGFR-TKIs application.Clinical intervention can be given in advance to provide patients with individual Treatment to prolong the survival of patients.