The Effect Of TP53 Gene Mutation On The Prognosis Of EGFR Mutant Advanced Non-small Cell Lung Cancer Patients

Background: Lung cancer is a global health problem with the highest mortality rate among malignant tumors worldwide.According to the 2020 global cancer statistics released by the International Agency for Cancer Research in 2022,there were approximately 820000 newly diagnosed lung cancer cases and 715000 deaths related to lung cancer in China in 2020.With the development of second-generation sequencing technology,EGFR has been found to be the most common type of gene mutation in NSCLC patients.The survival period of NSCLC patients with EGFR mutations was significantly prolonged after treatment with EGFR-TKI,but those with EGFR gene mutations combined with other gene mutations had a shorter survival period.TP53 gene mutation is a common comorbid mutation in NSCLC patients with EGFR gene mutations.Objective: To investigate the effects of TP53 and its different mutant subtypes on the2-year survival rate and progression free survival(PFS)of advanced non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutations.Method: A retrospective study was conducted on 119 late stage NSCLC patients diagnosed with EGFR gene mutations confirmed by pathological examination and Next generation sequencing(NGS)at Yan’an University Affiliated Hospital from January 2017 to December 2020.Collect general information,clinical pathological information,and genetic testing data of patients through browsing past medical records,telephone followup,and outpatient follow-up(all provided by Shaanxi Baimei Medical Laboratory).Follow up was conducted on 119 patients included in this study,including their disease progression and survival status(time of death,cause of death).The endpoint of the study was 2-year survival rate and PFS,and the follow-up deadline was December 31,2022.The data was analyzed using SPSS 26.0 statistical software.Chi-square test was used to analyze different variable groups among groups.Kaplan Meier method was used to analyze 2-year survival rate and PFS,and survival curves were plotted.Log rank method was used for univariate significance test,and Cox regression model was used for multivariate analysis.When P<0.05,statistical significance was considered for the differences.Results: 1.The mutation rate of TP53 gene was 60.5%(72/119)in 119 NSCLC patients with EGFR mutation positive included in this study.TP53 mutations mainly occurred in DNA binding domain(DBD)(52/72,72.2%),and missense mutation were more common(45/72,62.5%).There is an association between TP53 mutations and age and smoking history(P<0.05),and patients aged ≥ 60 years with a smoking history have a higher frequency of TP53 mutations.2.The survival analysis results of EGFR mutant NSCLC patients showed that compared to patients with only EGFR mutation and TP53 mutation,the 2-year survival rate was worse(P=0.028);Patients with a history of smoking have a worse 2-year survival rate than those without a history of smoking(P=0.009);Patients with a Group performance status(PS)of 2 had a worse 2-year survival rate compared to patients with a PS of 0-1(P=0.005).Patients aged ≥ 60 years have shorter PFS(P=0.014).In the survival analysis of TP53 wild-type compared to different subtype mutations,TP53 DBD mutation was an independent risk factor for 2-year survival in EGFR mutant advanced NSCLC patients(P=0.031);TP53 non missense mutation had worse 2-year survival rate than TP53 wild type(P=0.007);The TP53 destructive mutation had a worse 2-year survival rate compared to the TP53 wild-type(P=0.009).3.Survival analysis was conducted on patients with EGFR/TP53 co mutation,and the results showed that smoking history and a PS score of 2 were independent risk factors affecting the 2-year survival rate of co mutation patients(P<0.05).A history of smoking,a PS score of 2,and rare exon mutations in EGFR are independent risk factors for PFS in co mutated patients(P<0.05).TP53 destructive mutations have a worse 2-year survival rate compared to TP53 non destructive mutations(P=0.011).Conclusion:1.TP53 mutation is an independent risk factor for 2-year survival in EGFR mutant NSCLC patients.2.In patients with EGFR mutation,compared with TP53 wild group,TP53 DBD mutation group,TP53 non missense mutation group,and TP53 destructive mutation group had worse 2-year survival rate.3.Among EGFR/TP53 co mutation patients,the TP53 destructive mutation group had a worse 2-year survival rate than the TP53 non destructive mutation group.