Correlation Analysis Between Driver Genes Mutation And Clinical Features In 102 Cases With Advanced Non-Small Cell Lung Cancer

Objective:To investigate 102 cases with advanced non-small cell lung cancer with EGFR,ALK,KRAS,BRAF,ROS-1,RET,HER2,c-MET 8 common lung cancer driving genes are detected by next-generation sequencing.To evaluate the correlation between genes mutation and clinical characteristics in 102 cases with sensitive genes.To comparatively analyze the difference in efficacy and security between targeted therapy and chemotherapy.Methods:In this study,we examined the EGFR,ALK,KRAS,BRAF,ROS-1,RET,HER2,c-MET mutational status in 102 NSCLC cases detected by next-generation sequencing from January 2016 to June 2018 in the Second Hospital of Jilin University and analyzed the relationship between the driver genes status and clinical features.Comparative analysis of the discrepancy both objective response rate and disease control rate in patients who were positive for EGFR received targeted therapy or chemotherapy.Results:Within the 2155 patients with advanced NSCLC,102 patients were tested lung cancer-driven genes using the next-generation sequencing,and the detection rate was only 4.7%(102/2155).All patients were tested for EGFR,ALK,KRAS,BRAF,ROS-1,RET,HER2,and c-MET.There were 66 patients(66/102,64.71%)who underwent single-drive gene mutation,of which 46 patients had EGFR mutation,the rate was 45.10%(46/102);6 patients had ALK gene mutation.The mutation rate was 5.88%(6/102);8 patients had KRAS gene mutation,the mutation rate was 7.84%(8/102);1 patient had BRAF gene mutation,the mutation rate was 0.98%(1/102);There were no ROS-1 positive patients,therefore,the mutation rate was 0;1 patient was RET gene mutation,the mutation rate was 0.98%(1/102),which was KIF5B-RET fusion;3 patients were HER2 gene positive,mutation rate was 2.94%(3/102),1 patient was c-MET amplification,the incidence rate was 0.98%(1/102);double driving gene mutation were 3(3/102,2.94%);There were no cases with three or more driving gene mutations or amplifications.Of the 46 cases with positive EGFR mutations,42 had single-point mutation(42/46,91.30%),including 19-point deletion mutation(20/46,43.48%)and 21 exon L858 R mutation(14/46,30.43%),and another 4 patients had exon 20 mutation,and 1 patient had exon 18 mutation.Four patients had double-site mutations(4/46,8.70%),three in 19/20 exon mutations and one in 21/20 exon mutations.Six patients had ALK gene mutations,of which 5 were EML4-ALK fusion genes,accounting for 83.33%(5/6),and the other one was positive for KIF5B-ALK fusion gene.The EGFR mutation occurred more in women(p=0.045),adenocarcinoma(p=0.027),non-smokers(p=0.034),and there were no statistical differences in age,primary site,anatomical site,and TNM staging at the time of initial diagnosis.The ALK mutation occurred mostly in male patients(p=0.046).There was no statistical significance in smoking history,pathological type,age,primary site,anatomy site,and TNM staging at the time of initial diagnosis.The KRAS mutation occurred in patients with stage II TNM stage(p=0.043)at the time of initial diagnosis.The mutation rate in adenocarcinoma patients was higher than that in non-adenocarcinoma patients(7.95% vs.7.14%),but there was no statistics significance.There was no statistical difference in smoking history,age,gender,primary site,and anatomical site either.Three HER2 mutations were found in patients with adenocarcinoma.There was 1 case of BRAF,RET and c-MET gene mutation repectively,who all were non-smoking,female,and adenocarcinoma patients.There were no patients with ROS-1 gene mutations in 102 patients.Due to the lower mutation rate of HER2,BRAF,RET,c-MET and ROS-1 genes,the number of patients enrolled was less and the clinical data was limited.No statistical analysis was performed in this study.Of the 42 patients with positive EGFR mutations,33 patients in the targeted therapy group had an objective response rate(ORR)of 75.76%(25/33)and a disease control rate(DCR)of 90.91%(30/33).By contrast,9 patients in the themotherapy group,the objective response rate(ORR)was 33.33%(3/9),the disease control rate(DCR)was 55.56%(5/9).The adverse reactions in the targeted treatment group of EGFR gene mutation patients were mostly manifested in gastrointestinal reactions,liver dysfunction,and skin lesions,mostly 1-2 grades.After symptomatic treatment,they will soon recover;However,the chemotherapy group was poor.The response was mostly manifested in myelosuppression,liver dysfunction and gastrointestinal reactions,mostly mild,but 3-4 grades of toxicity occurred occasionally.The target group had significantly higher ORR(p=0.041),DCR(p=0.028)and lower incidence of adverse reactions(p=0.027),indicating that targeted therapy is superior to the chemotherapy group in efficacy and safety.Conclusion:1.There is a certain correlation between EGFR mutation in advanced NSCLC and gender,pathological type,and smoking history.Mostly occur in women,adenocarcinoma,and non-smokers.2.ALK mutation has a certain correlation with gender,more common in male.3.KRAS mutation can coexist with EGFR mutation.4.Statistically,the target group had significantly higher ORR,DCR and lower incidence of adverse reactions than the chemotherapy group.5.Next-generation sequencing can be applied to the detection of driver genes mutation with advanced NSCLC.