The Clinical Research On Gene Detection And Targeted Therapy With 76 Cases Of Lung Adenocarcinoma By The Second-generation DNA Sequencing Technology (NGS)

Purpose and Background:In recent years,next generation sequencing technology(NGS)known as high-throughput sequencing technology,has achieved rapid development and played a significant role in the treatment of diseases in the field of oncology.To interpret the relevant data obtained from NGS to guide the clinical treatment and prognosis and provide a theoretical basis,we analyzes 76 cases of lung adenocarcinoma by NGS detection of different specimens of hot spots related genes and targeted therapy for clinical research.Metheod:We collecte 76 patients with lung adenocarcinoma detected by the second generation DNA sequencing technique from China-Japan union hospital of JILIN university from January 2016 to November 2017.By observing the patient’s sex,age of onset,smoking,treatment history,physical status,family history of cancer,clinical stage,type of genetic test specimens,test results,treatment options and the efficacy after treatment.Statistical analysis was performed using SPSS19.0 software.The difference was statistically significant at P<0.05.Results:we find that the 76 patients with lung adenocarcinoma,32(42.11%)were male and 44(57.89%)were female,with a significantly greater number of females than males,with a median age of 64 years.Age ≥60years old and <60 years old accounted for 65.79%,34.21%.Smoker and non-smoker accounted for 35.53% and 64.47%,respectively,and nonsmokers were significantly higher than smokers(P = 0.01).There were 66 cases(86.84%)with ECOG score ≤1 point and 10 cases(13.16%)with ≥2 point score.Three cases(3.95%)were in stage IIIB and 73 cases(96.05%)in stage IV.There were 13 cases(17.11%)with family history of cancer and 63 cases(82.99%)with no history of family history of cancer.The rates of initial treatment,radiotherapy and chemotherapy were 73.68%,11.84%,14.48%,most patients with early treatment.In the46 tissue tests,there were 42 mutations(91.30%).In the 28 peripheral blood tests,there were 17 mutations(60.71%).And the pleural fluid test 9times,a mutation 8 times(88.89%).The positive rate of tissue test mutation was higher than that of peripheral blood(P = 0.00).Pleural effusion positive rate of mutation detection is also higher than peripheral blood,and tissue similar.Peripheral blood in the three specimens detected the lowest positive rate of mutation,the highest tissue.A total of 94 common lung adenocarcinoma gene changes,an average of 1.24 per patient found genetic changes.A total of 56 gene mutations were found in56 newly diagnosed patients,averaging 1.16 cases per case.A total of 29 genes were found in 20 patients(including chemoradiotherapy and targeted therapy),with an average of 1.45.The positive rates of EGFR,MET,KRAS,HER2,BRAF,PIK3 CA,ALK,ROS1 and RET were53.19%,15.96%,11.70%,8.51%,4.26%,2.13%,2.13%,1.06% and1.06%,respectively.The group of patients that could assessed the abundance of tissue mutations is in 42,the minimum is 3%,an average of29.55%.There were 18 mutations in blood abundance could be assessed,≤ 1% accounted for 7,an average of 11.52%.Abundant pleural fluid mutations can be assessed was 11,the average 19.55%.Tissue DNA mutation abundance was higher than blood,pleural effusion abrupt abundance,P was 0.00,pleural effusion mutation abundance higher than blood(P = 0.19).A total of 11 cases of KRAS mutations were found and found no coexistence with EGFR.BRAF mutation in 4 cases,were non-smoking patients,3 females.In the newly diagnosed patients,one case of positive coexistence of EGFR gene mutation and ALK gene fusion was found,one case of EGFR20 exon V774M(rare site)gene mutation and one case of ALK gene fusion positive and KRAS gene mutation co-existed after chemotherapy.The PFS of EGFR19/21 exon alone mutation group extended 2.8 months(11vs8.2)significantly compared with the group that combined with MET after trement of EGFR-TKI.There were 3 cases of PFS could be determined in the sevenpatients with Osimertinib up to the date of follow-up,with an average of5.3 months.It remained 4 patients who continued to benefit from three generations of TKI,none of them achieved PFS.One case of Crizotinib was positive for ROS1 gene fusion,and PFS was 8 months.Conclusion:1.lung adenocarcinoma was more common in female and nonsmoking patients.2.The positive rates of EGFR,MET,KRAS,HER2,BRAF,PIK3 CA,ALK,ROS1 and RET in the group of lung adenocarcinoma were 53.19%,15.96% and 11.70%,8.51%,4.26%,2.13%,2.13%,1.06%,1.06%.The positive rate of EGFR gene mutation was highest,and MET,KRAS,HER2 mutation were higher,too.3.Different specimens of the positive rate of gene mutation was that the tissue was higher than the pleural effusion,which was higher than the blood,while the mutation abundance of tissue higher than the pleural effusion,pleural effusion than blood,it was recommended we should prefered tissue samples by the NGS.Necessary,any two kinds of specimens matching test to improve the detection rate.4.It suggested that the tumor heterogeneity would be increased with the extension of treatment,we found that the account of gene mutation on patients with trement(target therapy,chemotherapy,radiotherapy)was more than cure treatment.It need to expand the sample to confirmedfurther.5.The PFS of patients with combined MET amplification compared with EGFR alone was significantly shortened after the first generation of EGFR-TKI treatment,indicating that MET amplification effects the efficacy of TKI.It need to expand sample to support the conclusion.6.NGS would play an important role increasingly in guiding treatment,assessing curative effect and judging prognosis on treatment of lung cancer.