Screening Of Key Genes And Pathways In Colorectal Cancer Based On Bioinformatics Analysis

Objective: Colorectal cancer(CRC)is a common malignant tumor with high morbidity and mortality worldwide.The purpose of this study is to screen and analyze the key differential genes and their related pathways between colorectal cancer and normal control tissues by bioinformatics,and to explore their effects on the pathogenesis of colorectal cancer,so as to provide a theoretical basis for the diagnosis and treatment of colorectal cancer,more in-depth understanding of the role of potential targets in colorectal cancer.Methods: Firstly,we selected the datasets of GSE9348,GSE21510,GSE21815 and GSE32323 gene expression profiles from GEO database,and screened the differentially expressed gene(DEGs)between colorectal cancer and normal tissues by GEO2 R platform.Then the GO and KEGG functional enrichment analysis of DEGs was carried out by using Fun Rich software and online functional annotation tool DAVID.The PPI network of DEGs was constructed by using STRING database and Cytoscape software,and the Top 15 key genes(Hub gene)which played an important role were screened and identified from PPI network.Finally,the prognosis of CRC was analyzed by using GEPIA online website,and the expression level of Hub gene in CRC was analyzed.Results: A total of 912 common DEGs were obtained,including 647 upregulated DEGs and 265 downregulated DEGs.The results of GO analysis showed that in terms of cellular component(CC),DEGs was mainly enriched in nucleolus,nucleoplasm,extracellular,chromatin,microtubule,etc;In terms of molecular function(MF),DEGs was mainly enriched in chemokine activity,extracellular matrix structural constituent,metallopeptidase activity,DNA-directed RNA polymerase activity,peptide hormone and so on;In the aspect of biological process(BP),DEGs is mainly concentrated in the regulation of cell cycle,cell proliferation,spindle assembly,mitosis,regulation of cell proliferation and so on.KEGG pathway analysis shows that DEGs is mainly related to cell cycle,DNA replication,mineral absorption,ribosome biogenesis in eukaryotes,p53 signaling pathway,pancreatic secretion,aldosterone-regulated sodium reabsorption,purine metabolism,proximal tubule bicarbonate reclamation,pyrimidine metabolism,nitrogen metabolism,ECM-receptor interaction,protein digestion and absorption,TGF-β signaling pathway,RNA transport and so on.We constructed a PPI network consisting of 133 nodes and 2082 edges,and identified Top15 Hub genes: CDK1,NCAPG,CCNB1,CCNA2,BUB1,RRM2,TTK,MAD2L1,AURKA,BUB1 B,TOP2A,NUSAP1,TPX2,ASPM,KIF20 A.According to the survival analysis of Hub gene,it was found that NCAPG,CCNA2,BUB1,RRM2,MAD2L1 and AURKA were related to the overall survival(OS)or disease free survival(DFS),and the difference was statistically significant.The OS of CRC patients with higher NCAPG,CCNA2,BUB1,MAD2L1 and AURKA gene expression levels was significantly longer than that of CRC patients with low expression levels,and the DFS of CRC patients with higher RRM2 and AURKA gene expression levels was significantly longer than that of CRC patients with low expression levels.The expression of the selected genes was analyzed by GEPIA online website,the results showed that compared with the normal control tissue samples,the selected genes(NCAPG,CCNA2,BUB1,RRM2,MAD2L1 and AURKA)were highly expressed in COAD and READ tissue samples.Conclusion: In conclusion,this study screened and analyzed the DEGs between the primary lesions of CRC patients and normal control tissues by comprehensive bioinformatics,and explored the role of DEGs in the carcinogenesis,progresssion and prognosis of CRC.Consequently,912 common DEGs were screened out,NCAPG,CCNA2,BUB1,RRM2,MAD2L1 and AURKA of Top 15 Hub gene are highly expressed in CRC patients and positively correlated with OS or DFS.It is expected to provide some reference value for clinical diagnosis and treatment,but its specific mechanism still needs to be verified by further experimental research.