Study On The Driver Gene Mutations And Clinicopathological Characteristics Of Stage ? Invasive Lung Adenocarcinoma

Object:In the past ten years,the biological and clinical features of lung cancer,such as epidermal growth factor receptor(EGFR)and other common driver gene mutations,have been thoroughly studied.Targeted treatment based on advanced lung adenocarcinoma research The curative effect is related to driver gene sensitive mutations.In recent years,the frequency of early diagnosis of lung cancer has been increasing.However,there is insufficient research on the status of driver genes and clinicopathological characteristics of patients with pathological stage ? invasive lung adenocarcinoma.It is not clear whether the patients with sexual lung adenocarcinoma can benefit.Therefore,this study intends to retrospectively analyze the distribution of driver genes and clinical pathological characteristics of stage ? invasive lung adenocarcinoma,in order to understand the characteristics of driver genes in the development of stage ? invasive lung adenocarcinoma,and to deepen our Understanding of biological behavior,and provide a theoretical basis for guiding postoperative adjuvant treatment of pathological stage ? lung infiltrating adenocarcinoma.Methods:We retrospectively included 83 patients with stage ? invasive lung adenocarcinoma who underwent radical surgery at the First Affiliated Hospital of Soochow University from October 2017 to August 2019.Collect and record the clinicopathological data of patients and the lung cancer driver gene status and mutation information detected by Illumina Solexa second-generation sequencing platform.Analyze the status of driver gene mutations in patients included in the study,and analyze the correlation with clinicopathological characteristics.All statistical analyses were performed using SPSS 19.0 statistical software.Counting data was chi-square test or Fisher's exact test.Measurement data was independent sample t test or rank sum test with mean ± standard deviation.EGFR 21 exon mutations were distinguished by age The cut-off value for non-21 exon mutations was determined by ROC curve analysis,and the independent risk analysis of related factors and EGFR 19 exon mutations was by Logistic regression analysis.P<0.05 indicated that the difference was statistically significantResults:1.A summary of the results of driver gene mutations in stage ? invasive lung adenocarcinoma showed that the total mutation rate was 85.5%(71/83),of which the EGFR gene mutation rate was 68.7%(57/83);the TP53 gene mutation rate was 9.6%(8/83);BRBB2(HER2)gene mutation rate was 6.0%(5/83);RET gene mutation rate was 4.8%(4/83);EML4-ALK gene mutation rate was 3.6%(3/83);KRAS The gene mutation rate was 3.6%(3/83);no mutations were detected in BRAF and MET genes.Of all patients with EGFR mutations,20(35.1%)had mutations in exon 19,27(47.4%)had mutations in exon 21,and 9(15.8%)mutations occurred in 18 and 20 Exons may be multiple mutations,and the types of mutations are mainly missense mutations,deletion mutations and insertion mutations.In all patients with TP53 gene mutation,a total of 8 different mutations were found,and the mutation types were missense mutations.The mutation sites are concentrated between 5 exons and 8 exons.Of the 71 patients with driver gene mutations,51 patients had single gene mutations,accounting for 71.8%;20 patients had polygenic mutations.accounting for 28.2%.Among them,EGFR was accompanied by other gene mutations in 16 cases,accounting for 22.5%.The most common concomitant mutation gene was TP53,a total of 6 cases,2 cases of RET concomitant mutation,1 case of ROS1 concomitant mutation,1 case of BRBB2(HER2),KRAS at the same time With EGFR mutations,no EML4-ALK fusion is accompanied by EGFR mutations.One case of TP53 single gene mutation was accompanied by 7 cases of other gene mutations,and one case of TP53 was accompanied by KRAS mutation.2.Analysis of the correlation between EGFR gene mutation and clinicopathological characteristics showed that no significant factors were found.However,the differences between the EGFR 19/21 exon mutation group and the non-19/21 exon mutation group were analyzed separately.Single factor analysis showed that EGFR 19 in women,stage IB,and stage ? invasive lung adenocarcinoma with pleural invasion The exon mutation rate was higher(P=0.025,0.003,0.031).EGFR 21 exon mutation had a significant correlation with age(P=0.019),and the EGFR 21 exon mutation rate was higher in patients>61 years old(P=0.021).multivariate logistic regression analysis showed that gender(OR=5.526(1.106-27.616);P=0.037;1=female,0=male)was an independent risk factor for mutation of exon 19 of EGFR gene..3.The analysis of the correlation between TP53 gene mutation and clinicopathological characteristics showed that:TP53 gene mutation was related to pTNM stage.The TP53 mutation rate in patients with stage IA was 5.1%,and the TP53 mutation rate in patients with stage IB was 20.8%.=0.041).4.The analysis of the correlation between single gene and polygene mutations and clinicopathological characteristics showed that:no significant correlation factors were found in the correlation analysis results of all single gene and polygene mutations,and correlation analysis of EGFR single gene mutations and polygene mutations was not found Significantly related factors.Correlation analysis of EGFR with TP53 gene mutation also found no significant related factors.Conclusion:1.In this study,the most common driver gene mutations in stage ? invasive lung adenocarcinoma were EGFR,TP53,BRBB2(HER2),RET,EML4-ALK,and KRAS genes.Among them,the EGFR gene mutation rate was the highest,and EGFR was the most common 21 Missense mutations of the son;followed by the TP53 gene,whose mutation sites are mainly located in exons 5-8,which are widely distributed;in patients with stage ?invasive lung adenocarcinoma carrying mutations of driver genes,about a quarter The patient had multiple gene mutations,most of which were EGFR accompanied by other gene mutations.TP53 was the most common concomitant mutant gene of EGFR.2.EGFR 19 exon mutations are more likely to occur in women,stage IB,and stage ?invasive lung adenocarcinoma with pleural invasion;patients with stage ? invasive lung adenocarcinoma aged?61 years are more likely to have EGFR 21 exon mutations.3.Patients with stage IB invasive lung adenocarcinoma are more prone to TP53 gene mutation than stage IA.4.This study did not find the correlation between single gene mutation and polygene mutation,EGFR simple mutation and combined mutation,and EGFR accompanied TP53 gene mutation and clinicopathological characteristics.