Prognostic Significance of FOXC1 in Various Cancers: A Systematic Review and Meta-Analysis
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Forkhead box C1 (FOXC1), a member of the Forkhead box (Fox) transcription factor family, plays an essential role in lymphatic vessel formation, angiogenesis and metastasis. Observational studies examining the relationship between the protein biomarker FOXC1 and breast cancer prognosis have reported conflicting findings. This systematic review and meta-analysis evaluates the prognostic value of the FOXC1 expression in association with patient survival in breast cancer and other types of cancers in order to identify the overall prognostic effectiveness of FOXC1.
This study followed the guidelines established in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We conducted a broad search on the online bibliographic databases EMBASE, PubMed, Science Direct and Scopus, limiting search to publications from 2010 to 2018. The prognostic value was demonstrated by a random effects model meta-analysis using the hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS) in various cancer patients. The heterogeneity was measured by the I2 statistic. Publication bias and quality assessment for the selected articles was performed. Subgroup analysis was conducted based on the data available from the selected articles.
A total of 16 studies met the predefined selection criteria established for our systematic review and meta-analysis, with multiple studies using diverse methodologies and reported on differing clinical outcomes, falling under a common banner of FOXC1 expression and survival in cancer. Overall, we observed a statistically non-significant association between FOXC1 protein expression and patients survival (HR: 1.186 and 95% CI 1.122–1.255, p = 0.000, I2 = 88.83%).
In summary, FOXC1 protein expression indicated poor survival outcome in various carcinomas, especially in patients with breast cancer, suggesting it as a possible biomarker for the prognosis in multiple carcinomas. Further clinical evaluation and large-scale cohort studies are required to accurately identify its possible clinical utility.
We would like to acknowledge the Meta-Analysis Concepts and Applications Workshop Manual by Michael Borenstein for its guidelines on reporting meta-analysis, subgroup analysis and publication bias (www.meta-analysis-workshops.com).
Compliance with Ethical Standards
Conflict of Interest
Nadana Sabapathi, Shanthi Sabarimurugan, Madurantakam Royam Madhav, Chellan Kumarasamy, Xingzhi Xu, Gaixia Xu, and Rama Jayaraj declare that they have no conflicts of interest related to this systematic review.
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Ethics approval and consent to participate
Ethical approval is not a requirement because all data in this review were retrieved from published studies. Since there is no specific direct patient involvement, ethical committee approval is not required.
RJ, XX and GX conceived this study and provided supervision and mentorship to NS. RJ and NS led the development of the study design, wrote the first draft, and coordinated and integrated comments from co-authors XX, GX, SS, MRM and CK. The editing of the final draft were done by SS, MRM and CK. RJ provided methodological guidance on the overall development of the protocol. All authors read, refined and approved the final version of the manuscript.
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