A Study On Gene Screening Of Lung Adenocarcinoma In TCGA Database And Prognosis Of BUB1B MRNA Expression

Part I: screening and bioinformatics analysis of related genes of lung adenocarcinoma.Objective : Digging genes that are significantly associated with lung adenocarcinoma,To explore the pathogenesis of lung adenocarcinoma.Methods:This study explored the original expression data of mRNA in cancer tissues and paracancerous tissues of lung adenocarcinoma patients in the TCGA database.Screening for differentially expressed genes using R software combined with edgeR package(logFC >2 fold,P<1-4E),The first 100 significant up-regulated and down-regulated genes were selected for GO analysis,KEGG signaling pathway analysis,and protein interaction network analysis.Results : A total of 5589 genes were identified that were significantly associated with lung adenocarcinoma,of which 4,796 were up-regulated and 793 were down-regulated.The GO enrichment analysis yielded 12 items(FDR<0.01)indicating that these gene biological pathways are mainly enriched in mitotic nuclear division,cell division,angiogenesis,sister chromatid cohesion,mitotic sister chromatid separation,mitotic cytoplasm Division and chromosome separation;Molecular function mainly focuses on protein binding;The cell localization mainly consists of spindle,concentrated chromosome centromere,medium body,spindle microtubule.The KEGG pathway analysis revealed that these genes involved 12 pathways(P<0.01)and were mainly concentrated in the cell cycle,malaria,oocyte meiosis,p53 signaling pathway and other signaling pathways.Protein interaction network analysis results suggest that the protein at the central node of the network has: Topoisomerase IIα(TOP2A),kinesin superfamily 11(KIF11),cyclin B1(CCNB1),kinesin superfamily 20A(KIF20A),spindle checkpoint protein(BUB1B),mitotic centromere-associated driver Proteins(KIF2C),cyclin B2(CCNB2),cell division cycle related gene 8(CDCA8),centromere protein A(CENPA),maternal embryo leucine zipper kinase(MELK),etc.Conclusion:Through the Analysis of lung adenocarcinoma related genes by bioinformatics,it was found that the occurrence of lung adenocarcinoma may be related to the abnormal process of mitosis.Among them,TOP2 A,KIF11,CCNB1,KIF20 A,BUB1B,KIF2 C,CCNB2,CDCA8,CENPA,MELK and other genes may play an important role in the occurrence and progression of lung adenocarcinoma.Part II: correlation between the Expression of BUB1 B mRNA and clinical Features and Prognosis of Lung Adenocarcinoma.Objective:To investigate the relationship between the expression of BUB1 B mRNA and the clinical features and prognosis of lung adenocarcinoma,to further understand its important role in the progression of lung adenocarcinoma,and to provide new potential gene targets for the diagnosis and treatment of lung adenocarcinoma.Methods : The clinical data of patients with lung adenocarcinoma were obtained from the TCGA database and integrated with the data of the normalized BUB1 B mRNA expression during the differential expression analysis in the first chapter.A total of 501 samples were included.The high and low expression levels were distinguished by the median value of BUB1 B mRNA expression(591.71),using Chi-Square Test to Assess the Relationship between High Expression Rate of BUB1 B mRNA and clinical Features,Kaplan-meier method was used to analyze the relationship between variables and prognosis and to make survival curves.Multiple factor analysis using Cox proportional risk model;P<0.05 was considered statistically significant.Results:1.The median survival period of the whole group was 48.5 months(95%CI: 40.5 to 56.4 months),the 1-year survival rate was 89.0%,the 3-year survival rate was 62.1%,and the 5-year survival rate was 39.5%.2.The expression level of BUB1 B mRNA was significantly correlated with gender,age,clinical stage and lymph node metastasis(P<0.05),and no significant correlation with tumor size and distant metastasis(P>0.05).3.Univariate analysis showed that the overall survival rate of patients with lung adenocarcinoma after operation was significantly correlated with clinical stage,tumor diameter,lymph node metastasis,distant metastasis,and BUB1 B mRNA expression(P<0.05).There was no significant correlation with tumor size and distant metastasis(P>0.05).4.Multi-factor analysis showed that clinical stages(HR: 3.715,95%CI: 1.664-8.293,P=0.001)and BUB1 B mRNA expression(HR: 1.572,95%CI: 1.127-2.194,P=0.008)were independent risk factors for the prognosis of lung adenocarcinoma patients.5.According to the follow-up time,sex,age,clinical stage,T stage,N stage,M stages stratified analysis,found that "0-79 month follow-up time","male","≥65 years old ","I and II","T1 and T2","N0 and N1" "M0" in these subgroups BUB1 B mRNA expression level has significantly associated with overall survival(P < 0.05).However,there was no statistically significant difference in the other subgroups.Conclusion:1.The expression level of BUB1 B mRNA was closely related to gender,age,clinical stage and lymph node metastasis in patients with lung adenocarcinoma.2.BUB1 B mRNA expression can be an independent risk factor for prognosis of lung adenocarcinoma patients.