Bioinformatic Analysis Of Differentially Expressed Genes In Colorectal Cancer Liver Metastasis

Background: Colorectal cancer(CRC)is one of the most common malignancies worldwide.The majority of CRC related deaths result from liver metastases.At present,the differentially expressed genes(DEGs)of CRC liver metastasis are still unclear,and its molecular mechanisms still await clarification.Objective: To preliminarily understand the role of DEGs in CRC liver metastasis compared with primary leisons by bioinformatic analysis.Methods: We screened significant DEGs between CRC liver metastases and primary lesions from GSE41258 data set in the GEO database by GEO2 R platform.GO and KEGG analysis were applied by FunRich for the identification of functions and pathways in which DEGs significantly enriched.The PPI network was constructed by STRING,and the network was visualized and screened for the Hub genes by Cytoscape software.Genome Enriched Analysis(GSEA)was performed by using all the genes of the two groups through GSEA software.Finglly,we used Gene Expression Profiling Interactive Analysis(GEPIA)software to further analyze the prognostic values of Hub genes.Results: There were 263 DEGs in CRC liver metastases relative to the primary lesions.GO analysis results showed that the Top 6 of Cellular Component(CC)enriched by DEGs include: Extracellular space,Chylomicron,Very-low-density,Exosomes,Extracellular matrix,Platelet alpha granule lumen;the Top 6 of Molecular Function(MF)were significantly enriched in: Protease inhibitor activity,Complement activity,Transporter activity,Extracellular matrix,Chemokine activity,Polysaccharide binding;the Top 6 of Biological Process(BP)were significantly enriched in: Immune response,Energy pathways,Protein metabolism,Cell growth and/or maintenance,Transport,Complement activation;KEGG analysis found that the Top 6 pathways were significantly enriched in: Epithelial to mesenchymal transition,Formation of fibrin clot,Regulation of insulin-like growth factor(IGF)activity by insulin-like growth factor binding proteins(IGFBPs),FOXA transcription factor networks,Hemostasis,Lipid digestion,mobilization,and transport.GSEA showed that the Top 6 gene sets enriched of Negative regulation of receptor-mediated endocytosis,Rab guanyl-nucleotide exchange factor activity,Ionotropic glutamate receptor binding,Regulation of collateral sprouting,Actin polymerization or depolymerization,Glutamate secretion.The Top 10 Hub genes are separately ALB,APOB,F2,APOA1,FGA,SERPINC1,FGG,KNG1,AHSG,SERPINA1,which resulted from PPI network.2 genes screened from Hub genes affecting the disease-free survival(DFS)of CRC patients were ALB and SERPINA1,the DFS of patients with high expression of ALB and low expression of SERPINA was significantly shortened.Conclusion: There were 263 DEGs between the CRC liver metastases and the primary lesions.Top 10 Hub genes are ALB,APOB,F2,APOA1,FGA,SERPINC1,FGG,KNG1,AHSG and SERPINA1.Among them,ALB and SERPINA1 have the closest relationship with DFS of CRC,and it is expected to be markers for screening,treatment and prognosis of CRC liver metastasis,which is worthy of further experimental verification.