Identification of FOXM1 as a novel protein biomarker and therapeutic target for colorectal cancer progression: Evidence from immune infiltration and bioinformatic analyses

Int J Biol Macromol. 2024 Dec;282(Pt 4):137201. doi: 10.1016/j.ijbiomac.2024.137201. Epub 2024 Nov 1.

Abstract

Colorectal cancer (CRC) remains a major global health challenge, with its underlying molecular mechanisms, particularly the role of FOXM1, not yet fully understood. This study employed an integrated approach combining bioinformatics along with experimental validation to explore the role of FOXM1 in CRC. Using advanced computational tools and experimental techniques, we aimed to clarify the biological significance of FOXM1 and its potential impact on CRC progression and treatment. Bioinformatic analyses, including pan-cancer views, mRNA expression analysis, immune infiltrations, pathway enrichment, and functional annotations, highlighted the oncogenic potential of FOXM1 in CRC. Protein and gene expression analyses (western blot and qPCR) were conducted in HCT-116 and HT-29 cells. Platforms like GEPIA and UALCAN confirmed the diagnostic relevance of FOXM1, showing upregulated mRNA expression across various stages and metastasis. The influence of FOXM1 on immune cells, particularly CD4+, CD8+, and B cells, was significant, as revealed by immunohistochemistry. Protein-protein interaction analysis through STRING and CYTOSCAPE identified genes closely linked to FOXM1 in CRC. KEGG pathway enrichment suggested FOXM1's involvement in the p53 pathway, reinforcing its role in oncogenesis. Experimental validation confirmed elevated FOXM1 expression in HCT-116 and HT-29 cells. In summary, this study indicates that targeting FOXM1 could be a promising therapeutic strategy in CRC, emphasizing its importance in the molecular landscape of cancer progression.

Keywords: Colorectal cancer; Comprehensive bioinformatic analyses; FOXM1; Immune infiltration; Oncogene; Proteins; Therapeutic target.

MeSH terms

  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / immunology
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Computational Biology* / methods
  • Disease Progression*
  • Forkhead Box Protein M1* / genetics
  • Forkhead Box Protein M1* / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Protein Interaction Maps / genetics

Substances

  • Forkhead Box Protein M1
  • Biomarkers, Tumor
  • FOXM1 protein, human