Delineating the underlying molecular mechanisms and key genes involved in metastasis of colorectal cancer via bioinformatics analysis.

Abstract

Colorectal cancer (CRC) is considered the world's fourth most deadly cancer. Its metastasis is associated with poor prognosis and weakens the effects of treatment. However, the potential molecular mechanisms and key genes involved in CRC metastasis have remained to be comprehensively elucidated. The objective of the present study was to identify the key genes and molecular pathways underlying CRC metastasis. Differentially expressed genes(DEGs) between primary CRC tissues and metastatic CRC were identified by analyzing the GSE2509dataset from the Gene Expression Omnibus database. Subsequently, the DEGs were subjected to Gene Ontology(GO) term and Kyoto Encyclopedia of Genes and Genome(KEGG) pathway enrichment analyses via the Database for Annotation, Visualization and Integrated Discovery(DAVID). Next, the top ten hub genes were identified in a protein-protein interaction(PPI) network. Sub-network and pathway enrichment analysis were respectively performed with the plugin MCODE and DAVID. Finally, reverse transcription-quantitative polymerase chain reaction assays were performed to corroborate the expression levels of the top five potential metastasis-associated genes in the clinical samples of CRC patients. A total of 7,384DEGs were obtained, among which 3,949were upregulated and 3,435were downregulated. GO and KEGG enrichment analyses identified numerous possible biological processes and pathways that may have a role in the metastasis of CRC. The leading ten hub genes, recognized from the PPI, were epidermal growth factor receptor(EGFR), Has proto-oncogene GTPase(HRas), Wnt family member5A(Wnt5a), serine/threonine kinase1(Akt1), cyclin-dependent kinase inhibitor 1A(CDKN1a), early growth response1, Ras homolog family memberA, cyclinD1 and Ras-relatedC3 botulinum toxin substrate1. Sub-network analysis disclosed the most prominent three modules. Ultimately, EGFR, HRas and Akt1 were verified to be upregulated DEGs, while Wnt5a and CDKN1a were downregulated DEGs when compared with the primary controls. In conclusion, the present study revealed several key genes and relevant molecular mechanisms that may enhance the current understanding of CRC metastasis, making them significant potential foci for the discovery of further CRC treatments.