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Bioinformatics Analysis Of Colorectal Cancer Differentially Expressed Genes Based On TCGA Database

Posted on:2019-07-23Degree:MasterType:Thesis
Country:ChinaCandidate:C F LiFull Text:PDF
GTID:2370330623452346Subject:Internal medicine
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Objective: This study is based on bioinformatics analysis of colorectal cancer gene expression profile RNAseq data about the TCGA database.It is aim to explore the key genes and pathways related to the tumorigenesis?development and prognosis of colorectal cancer,which may provided references for a better understanding molecular mechanisms and prognosis monitoring of colorectal cancer.Methods: Downloading the RNAseq data of colorectal cancer from TCGA database.Using R-DESeq package screening differentially expressed genes,GO functional annotation analysis of differentially expressed genes by using DAVID online analytical database,KEGG pathway analysis of differentially expressed genes by using R-clusterProfiler package and R-pathview package,STRING database and Cytoscape software were used to draw differentially expressed protein encoded by gene interaction network diagram(PPI)and Preliminary identification of key genes and their signaling pathways related to colorectal cancer.The survival analysis of differentially expressed genes was carried out by R-survival package to screen of genes related to prognosis of colorectal cancer.Results:(1)4017 differentially expressed genes were found by the gene expression profiles of large samples of colorectal cancer,among which 1653 genes were up-regulate genes and 2364 genes were down-regulate.(2)GO functional annotation found upregulated differentially expressed genes of molecular functions involved mainly in protein binding ? serine-type endopeptidase activity and extracellular matrix structural constituent and the like;biological processes are mainly involved in the cell division?mitotic nuclear division?DNA replication and G1/S transition of mitotic cell cycle and other processes;there are major cellular components of nucleoplasm?proteinaceous extracellular matrix and nucleolus.At the same time,KEGG pathway analysis found that these up-regulated differentially expressed genes mainly involved in cell cycle?p53 signaling pathway?Ribosome biogenesis in eukaryotes?Complement and coagulation cascades and DNA replication.(3)GO functional annotation showed downregulated differentially expressed genes of molecular functions involved mainly in the heparin binding?receptor binding?receptor activity and adenylate cyclase binding;biological processes are involved in cell adhesion?positive regulation of cytosolic calcium ion concentration?muscle contraction and sodium ion transport process;there are major cellular components of plasma membrane?integral component of plasma membrane and integral component of membrane.KEGG pathway analysis found that these down-regulated differentially expressed genes mainly involved in Calcium signaling pathway?Circadian entrainment?Drug metabolism-cytochrome P450?Neuroactive ligand-receptor interaction?cGMP-PKG Signaling pathways etc.(4)The protein interaction network analysis showed that upregulated differentially expressed protein-coding gene construct networks found eight key genes(degree?20),respectively CDK1?CCNB1?BUB1?PLK1?TOP2A?PCNA?MAD2L1 and KIF20A;there are 10 key genes in the the downregulation of PPI network(degree?40),including GNG7?GNG13?GNG12?GNG2?ADCY9?ADCY5?LPAR1?BDKRB2?CASR and GNAI1.(5)The Kaplan-Meier survival analysis showed there are 17 genes associated with colorectal cancer prognosis obviously,BRIP1?CENPE?ABCD3?NAT2?AQP8?SUCLG2?GPD1L?GNG12?ABHD6?PARM1 and NIPAL1 were highly expressed,the survival time of patients with significantly increased;while the survival time of CDKN2 A,DMPK,MPP2,SGCA,NCS1 and SLITRK2 were significantly reduced.What is more,the 8 genes of ABCD3,DMPK,MPP2,SGCA,SUCLG2,NCS1,GNG12 and NIPAL1 were first identified.Conclusions:(1)Successfully screened colorectal cancer differentially expressed genes,and carried on its GO and KEGG pathway analysis to revealed the molecular function of differentially expressed genes and the related signal pathway,which provided a theoretical basis for the study of molecular mechanism involved in colorectal cancer.(2)Successfully constructed protein interaction networks of differentially expressed genes,selected CDK1?CCNB1?BUB1?PLK1?TOP2A?PCNA?MAD2L1?KIF20A?GNG7?GNG13?GNG12?GNG2?ADCY9?ADCY5?LPAR1?BDKRB2?CASR and GNAI1 are the key genes involved in colorectal cancer.(3)The survival analysis identified 17 genes,such as BRIP1,CENPE and CDKN2 A,which were significantly related to the prognosis of colorectal cancer.BRIP1,CENPE,ABCD3,NAT2,AQP8,SUCLG2,GPD1 L,GNG12,ABHD6,PARM1 and NIPAL1 were associated with better prognosis of colorectal cancer,while CDKN2 A,DMPK,MPP2,SGCA,NCS1 and SLITRK2 were associated with poor prognosis of colorectal cancer.This study would lay a theoretical foundation to clinical diagnosis and treatment of colorectal cancer provide new targets and prognostic markers.
Keywords/Search Tags:The Cancer Genome Atlas, colorectal cancer, differentially expressed genes, bioinformatics
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