Molecular mechanisms investigation for liver metastasis of colorectal cancer by combined bioinformatic gene expression profile analysis

Abstract

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. As the molecular mechanism for liver metastasis of CRC has not yet been completely discovered, identification of hub genes and pathways of this disease is of importance for revealing potential molecular mechanism of colorectal cancer progression. This study aimed to identify potential biomarkers and survival analysis of hub genes for CRC treatment. Methods: The differentially expressed genes (DEGs) between colorectal cancer liver metastasis and primary tumor were screened using microarray data from two datasets GSE179979, GSE144259 obtained from the Gene Expression Omnibus (GEO) database. Gene ontology (GO) and KEGG pathway enrichment analyses were performed for DEGs using DAVID database, the protein-protein interaction (PPI) network was constructed using the Cytoscape software, and module analysis was performed using MCODE. Then, overall survival (OS), progression free interval (PFI) and disease specific survival (DSS) analysis of hub genes was performed by using TCGA database. The correlations between hub genes and clinical values were validated through CRN and immunohistochemistry (IHC) stain. Results: A total of 64 DEGs were obtained, KEGG pathway analysis showed that the significant pathways included PPAR signaling pathway, Complement and coagulation cascades. Four hub genes (ITIH2, ALB, CPB2, HGFAC) and two biomarkers (CPB2, HGFAC) with significantly prognostic values were verified by Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) cohort. Conclusions: CPB2 and HGFAC may serve as new biomarkers in diagnosing liver metastasis of CRC or potential drug target.