Effect Of TP53 And EGFR Gene Co-mutation On The Efficacy Of EGFR-TKIs In Patients With Advanced Lung Adenocarcinoma

Backgroud Lung cancer is the most common malignant tumor in China and the world at present,and it is also the main cause of cancer death.About 80%-85% of them are non-small cell lung cancer.Currently,in the treatment model of non-small cell lung cancer,the research on driver gene is more and more common.A number of clinical studies have shown that,compared with the traditional two-drug chemotherapy with platinum,in terms of progression-free survival rate(PFS)and objective response rate(ORR),epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs has a significant advantage in first-line treatment of lung adenocarcinoma(LUAD)with EGFR gene mutation.However,recent studies have found that about 20-30% of lung cancer patients with EGFR gene mutations develop primary resistance to EGFR-TKIs.Therefore,it is particularly important to select relevant molecular biomarkers to predict the efficacy of EGFR-TKIs and guide subsequent treatment..Objective: To analyze the effect of TP53/EGFR gene co-mutation on the efficacy of epidermal growth receptor tyrosine kinase inhibitors(EGFR-TKIs)in lung adenocarcinoma patients.Methods: From January 2017 to August 2018,100 patients with advanced lung adenocarcinoma with EGFR gene mutation who visited the first affiliated hospital of anhui medical university,anhui provincial thoracic hospital and anhui provincial second people’s hospital and were definitely diagnosed(all confirmed by pathological examination)and treated with first-generation EGFR-TKIs were collected.The mutation of TP53 gene in advanced lung adenocarcinoma with EGFR gene mutation in 100 subjects was detected by next-generation sequencing method,and the results were statistically analyzed.Results: 1.The mutation rate of TP53 gene in 100 cases of advanced lung adenocarcinoma with EGFR mutation was 44.0%.There was no significant difference in the TP53 gene mutation between age,sex,smoking,clinical stage,and EGFR gene mutation status(P>0.05).2.TP53/EGFR gene co-mutation in patients with advanced lung adenocarcinoma treated with EGFR-TKIs compared with patients with EGFR-mutant lung adenocarcinoma,the median PFS was 3 months and 13 months,respectively,the difference was statistically significant.(P=0.000).3.Multivariate COX proportional hazard regression model analysis showed that TP53 gene was an independent predictor of PFS in patients with advanced lung adenocarcinoma of EGFR mutation receiving EGFR-TKIs(P=0.000).Conclusions: 1.In EGFR mutant advanced lung adenocarcinoma,TP53 mutation was not associated with age,gender,smoking history,clinical stage,and EGFR gene mutation types.2.In EGFR-mutant advanced lung adenocarcinoma,TP53 mutation is associated with poor prognosis in patients with lung adenocarcinoma and may be a predictors of EGFR-TKIs efficacy.