Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Nov 8:9:960698.
doi: 10.3389/fsurg.2022.960698. eCollection 2022.

FOXC2 as a prognostic marker and a potential molecular target in patients with human solid tumors

Long Zhang  1 , Yong He  1 , Xiaohong Tu  2 , Chao Wang  3 , Xiaojun Ding  1 , Rongqiang Ye  1 , Jiayu Shi  3   4 , Yuancai Xie  1 , Yufen Jiang  5 , Xiaohong Deng  1
Affiliations
Review

FOXC2 as a prognostic marker and a potential molecular target in patients with human solid tumors

Long Zhang et al. Front Surg. .

Abstract

Background: Forkhead Box Protein C2 (FOXC2) belongs to the Forkhead/Wing-helix family. The regulatory role of this transcription factor in physiological function and carcinogenic activity has been proven in subsequent investigations. However, there is still scarcity of evidence on the relationship between FOXC2 expression and prognosis in human solid tumors. We conducted this meta-analysis to evaluate the role of FOXC2 as a prognosis factor and a possible target marker in human solid tumors.

Methods: PubMed, Web of Science, Embase, and the Cochrane library database were all searched methodically. Eligible publications on FOXC2 in human solid tumors were gathered and reviewed. The effect sizes were calculated using pooled hazard ratios (HRs) or odds ratios (ORs) with the corresponding 95% confidence interval (CI). Statistical analysis was conducted with Stata SE12.0.

Results: This meta-analysis comprised 3,267 patients from 20 studies covering a variety of solid tumors. Increased FOXC2 expression was related to shorter overall survival (OS) (HR = 2.05, 95% CI: 1.73-2.42). High expression of FOXC2 is associated with lymph node metastases (OR = 3.33, 95% CI: 2.65-4.19), TNM stage (OR = 3.09, 95% CI: 2.00-4.78), and age (OR = 1.26, 95% CI: 1.06-1.50), according to the pooled ORs. However, no significant association was observed between the high expression of FOXC2 and sex, tumor size or tumor differentiation.

Conclusion: Increased expression of FOXC2 is associated with unfavored OS, lymph node metastases, TNM stage, and age. FOXC2 is a promising prognostic marker and a novel target marker in human solid tumors.

Keywords: FOXC2; prognosis; solid tumor; survival; tumor biomarker.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Literature search and selection flowchart.
Figure 2
Figure 2
Forest plots for the relationship between high FOXC2 expression and OS.
Figure 3
Figure 3
Forest plots for the relationship between FOXC2 overexpression and clinical and pathological characteristics. (A) Lymph node metastases, (B) TNM stage, (C) tumor differentiation, (D) patient age.
Figure 4
Figure 4
Sensitivity analysis regarding overall survival.
Figure 5
Figure 5
Publication bias in this meta-analysis.
See this image and copyright information in PMC

References

    1. Hargadon KM, Győrffy B, Strong EW. The prognostic significance of FOXC2 gene expression in cancer: a comprehensive analysis of RNA-seq data from the cancer genome atlas. Cancer Genet. (2021) 254–255:58–64. 10.1016/j.cancergen.2021.02.005 - DOI - PubMed
    1. Herman L, Todeschini AL, Veitia RA. Forkhead transcription factors in health and disease. Trends Genet. (2021) 37:460–75. 10.1016/j.tig.2020.11.003 - DOI - PubMed
    1. Xu J, Wang K, Zhang Z, Xue D, Li W, Pan Z. The role of forkhead box family in bone metabolism and diseases. Front Pharmacol. (2021) 12:772237. 10.3389/fphar.2021.772237 - DOI - PMC - PubMed
    1. Koch S. Regulation of wnt signaling by FOX transcription factors in cancer. Cancers. (2021) 13. 10.3390/cancers13143446 - DOI - PMC - PubMed
    1. Myatt SS, Lam EW. The emerging roles of forkhead box (fox) proteins in cancer. Nat Rev Cancer. (2007) 7:847–59. 10.1038/nrc2223 - DOI - PubMed