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Forkhead box protein O1 (FOXO1) and paired box gene 3 (PAX3) overexpression is associated with poor prognosis in patients with cervical cancer

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Abstract

Purpose

Forkhead box protein O1 (FOXO1) and paired box gene 3 (PAX3) have been reported to play an imported role in human cancers, but their role in cervical cancer has not yet been clarified. In this study, we evaluated the functional role of FOXO1 in cervical cancer cells and investigated the expression and clinical significance of FOXO1 and PAX3 in cervical lesions.

Methods

In vitro assessment of cell function by cell viability, migration, and invasion assays were performed on FOXO1-knockdown cervical cancer cells. Immunohistochemical (IHC) staining analyses of FOXO1 and PAX3 were performed with a tissue microarray (TMA). The clinical significance was evaluated by comparing the data with various clinicopathologic characteristics, including survival of patients with cervical cancer.

Results

In vitro results revealed that knockdown of FOXO1 is associated with decreased cell viability (p < 0.001), migration (p < 0.001), and invasion (p < 0.05), supporting the oncogenic role of FOXO1 in cervical cancer. FOXO1 and PAX3 expression was significantly higher in CIN (both p < 0.001) and cancer tissue (both p < 0.001) than in normal tissue. Multivariate analysis indicated that FOXO1 expression (hazard ratio 4.01 [95% CI 1.22–13.10], p = 0.021) and an advanced FIGO stage (hazard ratio 3.89 [95% CI 1.35–11.19], p = 0.012) were independent prognostic factors for overall survival.

Conclusions

This study reveals increased FOXO1 and PAX3 expression in cervical cancers and indicates an oncogenic role of FOXO1 in cervical cancer cells that correlates with poor patient survival.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seoul, 03722, South Korea

    Doo Byung Chay, Gwan Hee Han & Hanbyoul Cho

  2. Department of Obstetrics and Gynecology, Gangnam Severance Hospital, 20 Eonjuro 63-gil, Seoul, 06229, South Korea

    Sanghee Nam

  3. Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA

    Joon-Yong Chung & Stephen M. Hewitt

Authors
  1. Doo Byung Chay
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  2. Gwan Hee Han
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  3. Sanghee Nam
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  4. Hanbyoul Cho
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  5. Joon-Yong Chung
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  6. Stephen M. Hewitt
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Correspondence to Hanbyoul Cho.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Chay, D.B., Han, G.H., Nam, S. et al. Forkhead box protein O1 (FOXO1) and paired box gene 3 (PAX3) overexpression is associated with poor prognosis in patients with cervical cancer. Int J Clin Oncol 24, 1429–1439 (2019). https://doi.org/10.1007/s10147-019-01507-w

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  • DOI: https://doi.org/10.1007/s10147-019-01507-w

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