The Research Of Malignant Pleural Effusion And Matching Specimens In Non-small-cell Lung Cancer Patients By Next Generation Sequencing

BackgroundLung cancer is one of the most comnon malignant tumor in China,and the diagnosis and treatment of advanced non-small cell lung cancer patients are the main problems faced in the clinical.This research uses the next generation sequencing method for advanced NSCLC patients with malignant pleural effusion and matching specimens to detect the common drive gene mutatio,so as to compare the positive rates between malignant pleural effusion and matching tissue specimens,matching plasma specimens,and to compare the pros and cons of gene mutation of the three samples.And we want to analysis the clinical curative effect of using the corresponding targeted drugs.Method56 malignant pleural effusions of NSCLC were collected in June 2014 to December 2016(Each patient was extracted pleural effusion 250—500ml and 10ml,and cancer cells can be found in pleural effusion).And 34 patients was extracted plasma(10ml).33 patients was extracted tumor tissue samples.We detected the common gene positive rate in malignant pleural effusion by ARMS and NGS in patients with NSCLC.Analyze the results and the clinical curative effect of using the corresponding targeted drugs.ResultsAll of 56 patients were detected by ARMS and NGS,EGFR mutation rate were 50%and 53.6%respectively the two methods.Compared with the ARMS method,the NGS method's sensitivity of the EGFR gene mutation was 86.7%,specificity of 92.3%.ARMS detected 3 patients with mutations in the ALK fusion.However,4 cases were detected with ALK mutations using NGS,including 1 case of HIP1-ALK mutation.Specimens of 56 patients with malignant pleural effusion,34 cases with matching plasma specimens,33 cases with matching tissue samples,we use NGS to detect three kinds of specimen in common driver mutations.34 cases of pleural effusion and serum specimens detect the EGFR mutations in consistency of 82.3%.33 cases of pleural effusion and tumor specimens detect EGFR mutations in consistency of 66.7%.In 56 cases,31 cases accept EGFR-TKJ drug therapy.No statistically significant differences of the mPFS(12.1 months and 18 months,P?0.246)between patients with two parts positive or one part positive detected NGS in pleural effusion and serum specimens was observed.No statistically significant differences of the mPFS(10.0 months and 6.1 months,P?0.383)between patients with two parts positive or one part positive detected NGS in pleural effusion and tumor specimens was observed.Compared the curative effect of patients treatment with EGFR-TKI whose EGFR mutation abundance divided into two groups at 10%and 50%respectively detected by NGS.No statistically significant differences of the mPFS(P?0.0.830)between mutation abundance under 10%and mutation abundance above 10%.No statistically significant differences of the mPFS(P=0.739)between mutation abundance under 50%and mutation abundance above 50%.7 patients with double genes mutation and 24 patients with single gene mutations were treated with EGFR-TKI,and the median PFS(3.8 months and 13.0 months,P=0.253)was no significant difference between the two groups.Compared to ARMS method,NGS could find more rare gene mutation.ConclusionCompared with traditional ARMS method,based on the next generation sequencing technology test specimens of pleural effusion is feasible,and it can direct the targeted drug therapy,and can be able to find some different driving gene.Compared with tissue specimens,pleural effusion and serum detection of EGFR mutations has a high consistency,maybe these two can be added with tissue specimens tested.