Prognostic Significance of FOXC1 in Various Cancers

A Systematic Review and Meta-Analysis

Nadana Sabapathi, Shanthi Sabarimurugan, Madhav Madurantakam Royam, Chellan Kumarasamy, Xingzhi Xu, Gaixia Xu, Rama Jayaraj

Research output: Contribution to journalReview articleResearchpeer-review

Abstract

Background: 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. 

Methods: 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. 

Results: 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%). 

Conclusion: 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.

Original languageEnglish
Pages (from-to)695-706
Number of pages12
JournalMolecular Diagnosis and Therapy
Volume23
Issue number6
DOIs
Publication statusPublished - Dec 2019

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Forkhead Transcription Factors
Meta-Analysis
Survival
Neoplasms
Breast Neoplasms
Accidental Falls
Biomarkers
Bibliographic Databases
Confidence Intervals
Lymphatic Metastasis
Carcinoma
Publication Bias
Lymphatic Vessels
PubMed
Patient Selection
Observational Studies
Publications
Cohort Studies
Guidelines

Cite this

Sabapathi, N., Sabarimurugan, S., Madurantakam Royam, M., Kumarasamy, C., Xu, X., Xu, G., & Jayaraj, R. (2019). Prognostic Significance of FOXC1 in Various Cancers: A Systematic Review and Meta-Analysis. Molecular Diagnosis and Therapy, 23(6), 695-706. https://doi.org/10.1007/s40291-019-00416-y
Sabapathi, Nadana ; Sabarimurugan, Shanthi ; Madurantakam Royam, Madhav ; Kumarasamy, Chellan ; Xu, Xingzhi ; Xu, Gaixia ; Jayaraj, Rama. / Prognostic Significance of FOXC1 in Various Cancers : A Systematic Review and Meta-Analysis. In: Molecular Diagnosis and Therapy. 2019 ; Vol. 23, No. 6. pp. 695-706.
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abstract = "Background: 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. Methods: 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. Results: 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{\%}). Conclusion: 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.",
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Sabapathi, N, Sabarimurugan, S, Madurantakam Royam, M, Kumarasamy, C, Xu, X, Xu, G & Jayaraj, R 2019, 'Prognostic Significance of FOXC1 in Various Cancers: A Systematic Review and Meta-Analysis', Molecular Diagnosis and Therapy, vol. 23, no. 6, pp. 695-706. https://doi.org/10.1007/s40291-019-00416-y

Prognostic Significance of FOXC1 in Various Cancers : A Systematic Review and Meta-Analysis. / Sabapathi, Nadana; Sabarimurugan, Shanthi; Madurantakam Royam, Madhav; Kumarasamy, Chellan; Xu, Xingzhi; Xu, Gaixia; Jayaraj, Rama.

In: Molecular Diagnosis and Therapy, Vol. 23, No. 6, 12.2019, p. 695-706.

Research output: Contribution to journalReview articleResearchpeer-review

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T2 - A Systematic Review and Meta-Analysis

AU - Sabapathi, Nadana

AU - Sabarimurugan, Shanthi

AU - Madurantakam Royam, Madhav

AU - Kumarasamy, Chellan

AU - Xu, Xingzhi

AU - Xu, Gaixia

AU - Jayaraj, Rama

PY - 2019/12

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AB - Background: 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. Methods: 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. Results: 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%). Conclusion: 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.

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Sabapathi N, Sabarimurugan S, Madurantakam Royam M, Kumarasamy C, Xu X, Xu G et al. Prognostic Significance of FOXC1 in Various Cancers: A Systematic Review and Meta-Analysis. Molecular Diagnosis and Therapy. 2019 Dec;23(6):695-706. https://doi.org/10.1007/s40291-019-00416-y