Meta-analysis of the likelihood of FOXC1 expression in early- and late-stage tumors

Abstract

Background: Aberrations in the expression of the transcription factor forkhead box C1 (FOXC1) have been linked to a number of malignancies. Here, we characterized the relationship between FOXC1 and cancer progression by conducting a metaanalysis of studies that reported the frequency of FOXC1 expression in tumors of different stages (T1, T2, T3, T4). Materials and Method: Relevant articles were retrieved from the Medline database by searching for the terms "FOXC1" and "cancer"; then, the retrieved articles were reviewed individually, and studies that were of multivariate cohort design, evaluated FOXC1 expression via immunohistochemical staining, and assessed the relationship between FOXC1 expression and cancer T-stage were included in our meta-analysis. Results: Our search terms identified 128 studies, 5 of which met all inclusion criteria. A total of 850 tumor samples were evaluated in the 5 studies; 452 samples were from early-stage (T1-T2) tumors, and 398 were from late-stage (T3-T4) tumors. FOXC1 was expressed in 60.7% (516/850) of all samples, in 54.6% (247/452) of early-stage tumor samples, and in 67.5% (269/398) of late-stage tumor samples. When calculated relative to early-stage samples, the pooled risk for FOXC1 expression in late-stage samples was 1.238 (95% CI = 1.061-1.444, p = 0.007). Conclusions: The results from our meta-analysis of 5 studies indicate that FOXC1 is 23.8% more likely to be expressed in late-stage tumors than in early-stage tumors.

The Diverse Consequences of FOXC1 Deregulation in Cancer

“…Indeed, there is a strong association between FOXC1 and tumor staging, metastasis and overall survival in many other cancer types beyond BLBC and AML. Finally, one meta-analysis of several tumor types found that expression of FOXC1 was more likely to be expressed in late-stage tumors than those at an earlier stage, highlighting the potential association with disease progression [103]. Clearly, classification of tumors by FOXC1 expression may be a valuable diagnostic tool and potential prognostic indicator for diverse cancer types.…”

Foxc1

“…In a meta-analysis on the likelihood of FOXC1 expression in early-and late- stage tumors, the results demonstrated that the expression rate of FOXC1 is similar in different cancers, including gastric carcinoma, non-small cell lung cancer, breast cancer, and hepatocellular carcinoma. 29 However, considering the high expression rate of FOXC1 in TNBC, it may play a role in differential diagnosis when used in combination with other biomarkers. Therefore, it would be valuable to investigate whether FOXC1 staining could be used to distinguish TNBC metastasis from primary cancer.…”

Therapeutically Targeting Cancers That Overexpress FOXC1: A Transcriptional Driver of Cell Plasticity, Partial EMT, and Cancer Metastasis

“…Indeed, an excellent and comprehensive systematic review and meta-analysis on the prognostic role of FOXC1 in cancer concluded that FOXC1 expression in cancer is indicative of poor survival outcome (126). In support of FOXC1 playing a role in cancer progression, another meta-analysis reported that FOXC1 is 23.8% more likely to be expressed in late-stage cancers as opposed to early-stage cancers (127). Below, we highlight those studies that demonstrate the role of FOXC1 in predicting an aggressive clinical course, specifically highlighting its role as a predictor of metastatic recurrence.…”