Apply Next Generation Sequencing In Detecting Driver Gene Mutation In Plasma In Advanced-stage Lung Cancer Patients

Objects: The purpose of the study was to investigate the clinical value of next-generation sequencing in advanced lung cancer patients by comparing driver gene mutationsbetween matched tissue and plasma.Methods:Patients suspected of advanced lung cancer were enrolled into the studyprospectively.Tissue samples underwent both conventional driver gene testing,including epidermal growth factor receptor(EGFR),anaplasticlymphoma kinase(ALK)and ROS proto-oncogene 1,receptor tyrosine kinase(ROS-1),and NGS testing.Plasma samples underwent NGS testing with the same panel,and then compare the driver gene mutationsbetween matched tissue and plasma.Clinical following-up was conducted for those who harbored sensitive driver gene mutations.Results:Forty patients were enrolled in the study.All the tissue and plasma samples underwent NGS test successfully.NGS has a good consistency with convential testing in tumor tissues,the consistency is 100%,97.5% and 100% in detecting EGFR,ALK and ROS-1.In advanced lung cancers patients,take the NGS results of tissue as reference,the sensibility and positive predictive value(PPV)of NGS in detecting gene mutations in plasma is 83.9% and 74.4%.Sensibility and PPV of the copy number amplifications(CNAs)are much lower than the other mutation types.Factors including sex,age,smoking history,pathological type and stage are no correlation with sensitivity and PPV.A good correlation of allelic fraction(AF)was found in matched tissue and plasma samples,particularly for those rich gene mutations in tissues.Forpatients who harbor sensitivity driver gene mutations in tissue and plasma can benefit from target therapy.Conclusions: NGS is a reliable techlogy,we can apply NGS in liquid biopsy instead of tissue biopsyin advanced lung cancer patients,the AF in plasma can reflects the AF in tumor tissue.Besides,the NGS results can predict the EGFR-TKI therapy response.