Background: The human epidermal growth factor receptor 2 (HER2) and transcription factor forkhead box protein M1 (FOXM1) are proto-oncogenes and have expressed in various kinds of human solid malignancies. However, the clinical significance of HER2 and FOXM1 in colorectal cancer (CRC) remains controversial, and there is no related report of the connection between HER2 and FOXM1 in colorectal cancer. This study aims to investigate the clinical values based on the connection of HER2 with FOXM1 in colorectal cancer.
Material/methods: We retrospectively investigated HER2 and FOXM1 expressions of 130 paraffin embedded CRC and their adjacent paraneoplastic tissues through immunohistochemical assay. Western blot and RT-PCR assays were applied to measure the relative expressions of HER2 and FOXM1 in mRNA and the protein levels of 30 fresh CRC and the adjacent paraneoplastic tissues.
Results: HER2 and FOXM1 expressions were significantly higher in colorectal cancer than those in paraneoplastic tissues (P<0.001). Similarly, the relative expression levels of HER2 and FOXM1 in mRNA and protein were also significantly higher in CRC tissues than those in paraneoplastic tissues (P<0.05). The HER2 expression was closely correlated with tumor size, degree of differentiation, presence of vascular invasion, lymph node metastasis, distant metastases, advanced TNM stage, and prognosis (P<0.05). The FOXM1 expression was related to tumor invasion, vascular invasion, lymph node metastasis, distant metastases, TNM stage, and prognosis (P<0.05). Besides, FOXM1 was an independent prognostic factor in CRC. There was a significant correlation between FOXM1 and HER2 expressions in colorectal cancer (r=0.335; P<0.01).
Conclusions: The overexpressions of HER2 and FOXM1 protein in colorectal cancer correlate with their clinicopathological characteristics and prognosis. HER2 and FOXM1 are important diagnostic markers for colorectal cancer. Furthermore, FOXM1 may be a potential target for therapy especially in HER2-targeted therapy-resistant cancers.
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