Study On The Relationship Between Gene Mutation Of Lung Cancer And Pathological Type Based On Large Data Mining

Objective:?To investigate the association between lung cancer gene mutation and pathologic type,to provide the theoretical basis for the pathological diagnosis of lung cancer,judgment of the malignancy,evaluation of the prognosis and selection of the individual treatment.?To compare the protein sequence of the first 20 mutant genes in lung cancer,to deduce the homologous genes,to verify the different pathological types of homologous mutations between the situation is consistent or not,to provide reference value for the study of gene function.Methods:?Combined with the COSMIC database,we obtained all the large sample mutation data of lung cancer,including mutation site,pathological type,all mutated genes and sample data of each mutation gene(point mutation,copy number variation,gene Expression and DNA methylation),the data were sorted and converted,using frequency analysis and composition ratio of large sample data for statistical description.? Mutation frequencies of the first 20 mutants(<5%)were screened based on the mutation frequency of each gene in the samples.The x2 test was used to analyze the association of the mutation,copy number variation,gene expression and DNA methylation with pathologic type,between the two groups were compared by using x2 segmentation.The protein sequences of the first 20 mutated genes were obtained by Uniprot protein database.The protein sequences were clustered by MEGA5.1 molecular evolution analysis software,and phylogenetic tree was constructed.Then the Boostrap method was used to verify the protein sequence.According to the similarity degree of each protein on the clustering map,the homologous gene was deduced,and the x2 test was used to analyze the mutations of the different pathological types ofhomologous genes.?K-means clustering method was used to cluster the first 20 mutated genes.Results:?The most frequently mutated genes were TP53(32.32%),followed by EGFR(29.12%).?The mutation rates of TP53,EGFR,KRAS,LRP1B,CDKN2A,STK11,FAT4,KMT2,KAMT2D,NFE2L2,KEAP1,PIK3CA,RBI,ERBB4,CREBBP and GRIN2A were different(P<0.05).?The copy number variability of KRAS,LRP1B,CDKN2A,KMT2C,FAT1,PIK3CA,RBI,ERBB4,GRIN2A and KDR were different(P<0.05).?The gene expression rate of TP53,KRAS,LRPIB,CDKN2A,STK11,FAT4,KMT2D,NFE2L2,KEAP1,PIK3CA,RBI,ERBB4,SMARCA4 and KDR were different(P<0.05).?CDKN2A showed hypermethylation of DNA,the remaining three genes were hypomethylated DNA,the DNA methylation incidence of FAT1 and GRIN2A is different among adenocarcinoma and squamous cell carcinoma samples.? The similarity of the protein sequence of EGFR and ERBB4 was 93%,the homology was high,and the similarity of FAT4 and FAT1 was 81%,the homology was good,and the Bootstrap value of the two groups was more than 70,the credibility is better.?For small cell carcinoma samples,there was no difference in point mutations and copy number variation between the two groups of homologous genes.There was no difference in point mutation and copy number variation between FAT4 and FAT1 genes in lung adenocarcinoma samples.For squamous cell carcinoma,there was no difference in point mutations between the two groups of homologous genes.?In the first 20 mutant gene samples,TP53 and EGFR were clustered into one class,PIK3CA was clustered into one class,and the other 17 genes were clustered into one class.Conclusion:?The point mutations,copy number variation,gene expression and DNA methylation of lung cancer-associated genes is related to pathologic types,and there are differences between the mutated genes.? EGFR and ERBB4 are homologous in the first 20 mutations of lung cancer,and FAT4 and FAT1 are homologous.?There were no differences in point mutations and copy number variation between the two groups of homologous genes in small cell carcinoma samples.There were no differences in point mutation and copy number variation between FAT4 and FAT1 genes in adenocarcinoma samples.There were no differences in the point mutations between the two groups of homologous genes in squamous cell carcinoma.