Evaluation of Forkhead BOX M1 (FOXM1) gene expression in colorectal cancer

Clin Exp Med. 2023 Oct;23(6):2385-2405. doi: 10.1007/s10238-022-00929-7. Epub 2022 Nov 1.

Abstract

Forkhead Box M1 (FOXM1)-a key cell cycle regulator is a member of the Forkhead transcription factor family. It plays a key role in embryogenesis and cell proliferation and has been strongly linked to various solid tumors. We sought to understand the regulation of FOXM1 in colorectal cancer (CRC), as well as if and to what extent other clinicopathological characteristics are associated with FOXM1. The investigation comprised 98 CRC samples and normal tissues (controls). All colon cancer patients had a colonoscopy and targeted biopsy. All rectal cancer patients had a CT and MRI. Real-time PCR, Immunohistochemistry, and Western blotting were used to evaluate FOXM1 expression, and the findings were analyzed using SPSS (v.26). FOXM1 mRNA and protein expression were substantially upregulated in tumor tissues, with the majority of these proteins localized in nucleo-cytoplasm. Elevated protein levels of FOXM1 were strongly correlated with lower education level, larger tumor size, lymph node status, lymphovascular invasion (LVI), perineural invasion (PNI), lymph node metastasis (LNM), tumor invasion depth (subserosal and serosal invasion), late stage (III and IV), localization (nucleo-cytoplasmic), intensity (strong) and recurrence. Based on survival analysis, FOXM1 overexpression and nucleo-cytoplasmic localization were associated with shorter disease-free survival while stage and PNI were linked to poorer overall and disease-free survival. According to the results of the Cox regression analysis, stage and PNI were significant predictors of prognosis in CRC patients. FOXM1 expression was elevated in CRC and was linked to reduced disease-free survival. These findings support prior reports and hence FOXM1 can be an important prognostic marker for CRC and a promising therapeutic target. Additionally, we found a link between poor disease-free survival and FOXM1's nucleo-cytoplasmic localization. However, since the sample size of this study was small, further research is needed to validate our findings.

Keywords: Colorectal cancer; Immunohistochemistry; Kashmir real-time PCR; Western blotting.

MeSH terms

  • Cell Line, Tumor
  • Colorectal Neoplasms* / pathology
  • Forkhead Box Protein M1* / genetics
  • Forkhead Transcription Factors / genetics
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Prognosis

Substances

  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • FOXM1 protein, human