Meta-analysis of the likelihood of FOXC2 expression in early- and late-stage tumors

BACKGROUND: Aberrations in the expression of the transcription factor forkhead box C2 (FOXC2) have been linked to a number of malignancies. Here, we characterized the relationship between FOXC2 and cancer progression by conducting a meta-analysis of studies that reported the frequency of FOXC2 expression in tumors of different stages (T1, T2, T3, T4). METHODS: Relevant articles were retrieved from the Medline database by searching for the terms “FOXC2” and “cancer”; then, the retrieved articles were reviewed individually, and studies that were of multivariate cohort design, evaluated FOXC2 expression via immunohistochemical staining, and assessed the relationship between FOXC2 expression and cancer T-stage were included in our meta-analysis. RESULTS: Our search terms identified 139 studies, 9 of which met all inclusion criteria. A total of 1433 tumor samples were evaluated in the 9 studies; 596 samples were from early-stage (T1-T2) tumors, and 838 were from late-stage (T3-T4) tumors. FOXC2 was expressed in 46.0% of all samples, in 32.4% of early-stage tumor samples, and in 55.6% of late-stage tumor samples. When calculated relative to early-stage samples, the pooled risk for FOXC2 expression in late-stage samples was 1.367 (95% CI = 1.103–1.695, p = 0.004). CONCLUSION: The results from our meta-analysis of 9 studies indicate that FOXC2 is 36.7% more likely to be expressed in late-stage tumors than in early-stage tumors.