Bioinformatics Analysis of Genes Related to Liver Metastasis of Colorectal Cancer

Abstract

Purpose: To find the key genes and therapeutic targets of liver metastasis of colorectal cancer (CRC) by mining and analyzing the existing gene expression data and related clinical data in the GEO database of the National Biotechnology Information Center (NCBI). Methods: The GEO database was searched, and the gene chips containing normal colorectal, CRC and liver metastatic tissues of CRC were screened. GEO2R tool was used to screen the differentially expressed genes (DEGs) between CRC and normal colorectal tissues and between CRC and liver metastasis of CRC, and the common DEGs of the two gene sets were further screened. Annotation, Visualization and Integrated Discovery Database (DAVID) was used for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis. STRING database and Cytoscape software were used to construct Protein-Protein Interaction (PPI) network and screen Hub genes. The expression of Hub genes in normal colorectal, CRC and liver metastatic tissues of CRC was analyzed by R language, and the correlation between Hub genes and the prognosis of CRC was analyzed by Gene Expression Profile Interactive Analysis (GEPIA) database. Results: The gene chip GSE49355 showed that there were 1394 genes in CRC and normal colorectal tissues, 125 genes in CRC and liver metastasis of CRC, and 29 DEGs in the two gene sets. GO analysis showed that their biological processes may be mainly concentrated in complement activation, positive regulation of polypeptidase activity, alternative pathway. Cellular components were mainly located in blood particles and peripheral cells. Molecular functions were enriched in peptidase activator activity, CXCR chemokine receptor binding, extra-cellular matrix binding and chemokine activity. The enrichment analysis of KEGG signal pathway showed that DEGs were mainly enriched in complement and coagulation cascade, IL-17 signal pathway and TNF signal pathway. According to the sequence of related genes in PPI analysis, the first five Hub genes were SPP1, MMP1, MMP3, CXCL1 and CXCL5. Their expression in CRC was higher than that in normal colorectal tissues. The expression of SPP1 was gradually increased in normal colorectal, CRC and liver metastatic cancer, and the high expression of SPP1 was significantly correlated with poor survival in patients with CRC. Conclusion: CRC liver metastasis is related to SPP1, MMP1, MMP3, CXCL1 and CXCL5, which may provide a basis for further research on the molecular mechanism of CRC liver metastasis.