• Deciphering Molecular Mechanisms of Colorectal Cancer Metastasis: A Comprehensive Bioinformatics Analysis of Dysregulated Genes and Pathways
  • Ahoura Haghi,1,* Mahdi Alaee,2
    1. Department of Biological Sciences and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran
    2. Shahid Rajaee Hospital, Qazvin University of Medical Sciences, Qazvin, Iran


  • Introduction: Colorectal cancer (CRC) metastasis is a complex process involving dysregulation of multiple genes and pathways. This study employs a bioinformatics approach to unravel the molecular mechanisms underlying CRC metastasis, focusing on the identification of dysregulated genes and enrichment of pathways associated with metastatic progression. Understanding these molecular alterations is critical for the development of targeted therapeutic interventions to combat CRC metastasis and improve patient outcomes.
  • Methods: Gene expression data from CRC patients with and without metastasis were retrieved from publicly available datasets, including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Differential gene expression analysis was performed to identify genes differentially expressed between metastatic and non-metastatic CRC samples. Functional enrichment analysis, including gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, was conducted to elucidate the biological processes and pathways dysregulated in CRC metastasis. Protein-protein interaction (PPI) network analysis was employed to identify key hub genes and potential regulatory networks associated with CRC metastasis.
  • Results: Analysis of gene expression data revealed a distinct gene expression signature associated with CRC metastasis, with numerous genes differentially expressed between metastatic and non-metastatic CRC samples. Functional enrichment analysis identified enrichment of biological processes related to cell adhesion, migration, invasion, and angiogenesis, highlighting their critical roles in metastatic progression. KEGG pathway analysis revealed dysregulation of pathways associated with epithelial-to-mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and PI3K-Akt signaling in metastatic CRC. PPI network analysis identified hub genes, including key regulators of metastasis such as MMP9, VEGFA, and CTNNB1, and revealed potential regulatory networks governing CRC metastasis.
  • Conclusion: This comprehensive bioinformatics analysis provides novel insights into the molecular mechanisms driving CRC metastasis. Dysregulated genes and pathways identified in this study offer potential therapeutic targets for intervention in CRC metastasis. Targeting key molecules involved in EMT, ECM remodeling, and angiogenesis may hold promise for inhibiting CRC metastasis and improving patient outcomes. Further experimental validation of identified biomarkers and regulatory networks is warranted to translate these findings into clinically relevant therapeutic strategies for CRC metastasis.
  • Keywords: Colorectal Cancer (CRC) Metastasis, Hub Genes, KEGG Pathway Analysis, PPI Network