Basic Features,Molecular Typing And Clinical Application Of Advanced Squamous Cell Lung Cancer Based On NGS Detection

Objective:The molecular typing of advanced squamous cell lung cancer was statistically analyzed by next generation sequencing(NGS)technology,and the basic characteristics and clinical data of patients were combined to guide the treatment,and the therapeutic effect was retrospectively analyzed to explore the feasibility of clinical application of advanced squamous cell lung cancer based on NGS technology.Methods:A total of 125 patients with advanced squamous cell lung cancer who were admitted to the First Affiliated Hospital of Nanchang University from January 2019 to June 2021 after screening and meeting the inclusion requirements were collected for NGS testing(by collecting the patients’ fresh tumor tissue,formalin fixed paraffin embedded,blood,pleural fluid,white tablets and other specimens),and then statistically and followed-up.By determining its molecular typing,10 patients with EGFR mutation and 2 patients with ALK fusion were treated,and their clinical data and efficacy were retrospectively analyzed.SPSS26.0 statistical software and Graph Pad Prism 9.0 were used for statistical analysis and mapping.Kaplan-meier method was used for survival time and log-rank method was used to test survival differences.Results:1.A total of 16 mutated genes and 150 mutated loci were detected in 105 mutated patients.An average of 1.43 gene mutations were detected per patient.The mutation rate of TP53 gene was higher(65%)and ranged from 4 to 10 exons.There were 69 single gene mutations,20 double gene mutations and 13 three or more gene mutations.The driving genes associated with the benefit of clinical targeted drugs included 11 EGFR mutation sites,including exon 18-21 mutation,mainly in exon 21L858 R mutation and exon 19 L747 deletion.ALK fusion 2;One exon mutation of ERBB2 20.The mutation probability of relevant driver genes for the benefit of clinical targeted drugs were EGFR(78.6%),ALK(14.3%),ERBB2(7.1%).The proportion of related driver gene mutations in the total number of cases was EGFR(8.8%),ALK(1.6%),ERBB2(0.8%).2.Pathological samples of 125 patients were collected and the number of gene mutations in each sample was analyzed,including 4 cases of white tablets,1 case of pleural effusion,18 cases of blood,and 82 cases of tissue/wax.After statistical analysis,P=0.000,the difference between squamous cell lung cancer mutation and sample type was statistically significant.Tissue and wax block group were used as the gold standard to compare the differences between white place-tissue/wax block,pleural effusion-tissue/wax block and blood-tissue/wax block groups.There was no statistically significant difference in the white tablet tissue/wax block group(P=1.000),pleural fluid tissue/wax block group(P=0.187),and blood tissue/wax block group(2=15.680,P=0.000).3.Among the 13 patients with driving genes related to the benefit of targeted drugs,age and bone metastasis groups showed no statistical significance(P >0.05).The probability of drug-related gene mutation in male patients was 5.3%,and that in female patients was 63.6%,P=0.000,the difference was statistically significant.The probability of drug-related gene mutation in patients with smoking history was 3.7%,and that in patients without smoking history was 22.2%,P=0.002,and the difference was statistically significant.4.According to the treatment of targeted drugs,10 patients with EGFR gene mutation were divided into the first and second generation EGFR-TKI treatment group(7 cases)and the third generation EGFR-TKI treatment group(3 cases),and the survival curve was plotted.Log-rank test results showed that the median PFS of the first and second generation EGFR-TKI group was statistically different from that of the third generation EGFR-TKI group(9 months vs.13 months,P=0.037 < 0.05).5.Among the 7 patients receiving primary and secondary EGFR-TKI,4 patients had EGFR mutation only,while the other 3 patients had TP53 mutation and EGFR amplification.They were divided into EGFR single gene mutation group and EGFR co-mutation group by driving gene,and the survival curve was plotted.Log-rank test results showed that there was no statistical significance in median PFS of EGFR single gene mutation group and EGFR co-mutation group(9 months vs 7 months,P=0.524 > 0.05).6.Among the 12 patients treated with targeted therapy,2 patients underwent another NGS test due to disease progression and drug resistance.Patient 1 was found to have increased EGFR mutation frequency after NGS test after gefitinib drug resistance,and the efficacy evaluation was PR after oral oxitinib single drug therapy,and the target lesion diameter was reduced by 51.7% compared with the previous one,and died of superior vena cava obstruction syndrome of lung cancer later.NGS test in patient 2 after drug resistance of Afatinib showed that the mutation frequency of EGFR decreased significantly,only 0.11%,while TP53 gene detected for the first time disappeared.Considering the low mutation frequency of EGFR,the treatment regimen was changed to TP combined with amitinib targeted therapy.He is still under treatment and has not yet been evaluated Conclusion:1.In the population with advanced squamous cell lung cancer,males aged ≥65,with a history of smoking and no bone metastasis are more common.2.Gene mutations in advanced SQUamous cell lung cancer are more common in patients without bone metastasis,while gene mutations benefiting from targeted drugs are more common in women and patients without smoking history.3.The gene mutation probability is higher in tissue/wax specimens than in blood specimens.4.For patients with advanced squamous cell lung cancer with EGFR mutation,the third generation EGFR-TKI has longer PFS than the first and second generation EGFR-TKI.5.NGS can dynamically detect gene mutations and frequency changes.