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Association of FOXA1 and EMT markers (Twist1 and E-cadherin) in breast cancer

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Abstract

The transcription factor FOXA1 (forkhead box A1) plays key roles in tumor development and progression. In the present study, we analyzed the expression of FOXA1 in 52 breast tumors and 10 normal tissues, and investigated the relationship between FOXA1 and two EMT markers, namely Twist1 and E-cadherin by RT-PCR and IHC respectively. The expression level of FOXA1 was higher in tumor compared to normal tissues but the difference was not statistically significant (P = 0.138). FOXA1 expression correlated with less aggressive behavior as SBR grade I (P = 0.04), small tumors size (P = 0.05), and longer survival (P = 0.001). Furthermore, estrogen and progesterone positive tumors exhibit high level of FOXA1 (P = 0.002 and P = 0.038 respectively). Survival analysis showed that patients with ER positive/FOXA1 positive (P log rank = 0.001), PR positive/FOXA1 positive (P log rank = 0.044) and HER-2 negative/FOXA1 positive (P log rank = 0.002) tumors have a significant prolonged overall survival. On the other hand, the expression of E-cadherin positively correlated with FOXA1 (P = 0.028), whereas negative association was seen between the expression of Twist1 and FOXA1 (P = 0.016). Kaplan–Meier plots showed that patients with Twist1negative/FOXA1positive tumors have a significant prolonged overall survival (P log rank = 0.001) and FOXA1 appeared as independent predictors of patient survival in multivariate analyses. Overall, our results indicate that FOXA1 could be a useful biomarker to predict prognosis in breast cancer patients.

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Acknowledgements

Authors thank technicians at CHU Habib Bourguiba at Sfax—Tunisia for assistance in immunohistochemistry experiments.

Funding

This study was supported by a Grant of the Tunisian Ministry of High Education and Scientific Research (Grant No: LR15CBS02).

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Authors and Affiliations

  1. Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour Street Km 6, BP 1177, 3038, Sfax, Tunisia

    Dorra BenAyed-Guerfali, Emna Dabbèche-Bouricha, Wajdi Ayadi & Raja Mokdad-Gargouri

  2. Institute of Biotechnology of Monastir, BP 223, 5000, Monastir, Tunisia

    Fatma Trifa

  3. Department of Anatomo-pathology, Habib Bourguiba Hospital, Sfax, Tunisia

    Slim Charfi & Tahia Sellami-Boudawara

  4. Department of Anatomo-pathology, Habib Bourguiba Hospital, Medenin, Tunisia

    Abdelmajid Khabir

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  1. Dorra BenAyed-Guerfali
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Contributions

DBG and EDB have conducted the experiments and analyzed the results. SC, AK, TSB analyzed the immunohistochemical slides and interpreted the results. WA, FT and RMG designed the work and helped in the interpretation of results. All the authors contributed to manuscript writing and approved it.

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Correspondence to Raja Mokdad-Gargouri.

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The authors declare that the Institutional Ethics Committee of the CHU Habib Bourguiba of Sfax –Tunisia, approved this study which was conducted in agreement with the recommendations of the Helsinki Declaration.

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Informed consent was obtained from patients included in the study.

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BenAyed-Guerfali, D., Dabbèche-Bouricha, E., Ayadi, W. et al. Association of FOXA1 and EMT markers (Twist1 and E-cadherin) in breast cancer. Mol Biol Rep 46, 3247–3255 (2019). https://doi.org/10.1007/s11033-019-04784-w

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