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Possible role of nuclear factor erythroid 2–related factor 2 in the progression of human colon precancerous lesions

  • Lorenzo Polimeno
    Affiliations
    Polypheno Academic Spin Off, University of Bari “A. Moro”, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy
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  • Maria Teresa Viggiani
    Affiliations
    Gastroenterology Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “A. Moro”, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy
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  • Floriana Giorgio
    Affiliations
    Gastroenterology Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “A. Moro”, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy
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  • Lucrezia Polimeno
    Affiliations
    Polypheno Academic Spin Off, University of Bari “A. Moro”, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy
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  • Deborah Fratantonio
    Affiliations
    Department of Biosciences, Biotechnologies and Biopharmaceutics, Campus Universitario “G. Quagliarello”, University of Bari “A. Moro”, 70125 Bari, Italy
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  • Marina Di Domenico
    Affiliations
    Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
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  • Mariarosaria Boccellino
    Affiliations
    Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
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  • Andrea Ballini
    Affiliations
    Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy

    School of Medicine, University of Bari Aldo Moro, 70124 Bari, Italy
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  • Skender Topi
    Affiliations
    Department of Clinical Disciplines, School of Technical Medical Sciences, University of Elbasan “A. Xhuvani”, Rruga Ismail Zyma, 3001 Elbasan, Albania
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  • Alfredo Di Leo
    Affiliations
    Gastroenterology Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “A. Moro”, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy
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  • Luigi Santacroce
    Affiliations
    Polypheno Academic Spin Off, University of Bari “A. Moro”, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy

    Department of Clinical Disciplines, School of Technical Medical Sciences, University of Elbasan “A. Xhuvani”, Rruga Ismail Zyma, 3001 Elbasan, Albania

    Department of Interdisciplinary Medicine, Microbiology and Virology Unit, Policlinico University Hospital of Bari, University of Bari Aldo Moro, 70124 Bari, Italy
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  • Michele Barone
    Correspondence
    Corresponding author at: Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Azienda Universitario-Ospedaliera Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy.
    Affiliations
    Gastroenterology Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “A. Moro”, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy
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Published:February 21, 2022DOI:https://doi.org/10.1016/j.dld.2022.01.131

      Abstract

      Background

      Increased levels of oxidative stress/cell inflammation contribute to colorectal cancer (CRC) onset. Nuclear factor-erythroid 2-related factor 2 (Nrf2) and its controlled growth factor erv1-like (Gfer) gene regulate redox‐sensitive and anti-inflammatory mechanisms, respectively, which can contribute to promoting cancer development.

      Aim

      We evaluated Nrf2 and Gfer RNA expression and Nrf2 protein expression in colon mucosa in order to establish their possible involvement in the early stage of CRC.

      Methods

      Forty subjects were enrolled after a histological evaluation of their colon biopsies. They included 20 subjects with a sporadic colorectal adenoma (SpCA group) and 20 without precancerous lesions (controls). Biopsy samples were processed for gene expression analysis and protein expression, using Real-time PCR and immunofluorescence confocal microscopy, respectively.

      Results

      Nrf2 and Gfer mRNA expression were significantly reduced (p=0.007 and p<0.003, respectively) in SpCA tissues compared to normal mucosa from controls. Furthermore, immunofluorescence analysis confirmed a relevant reduction of Nrf2 in SpCA tissue compared to normal tissue from controls.

      Conclusions

      Our data confirm the hypothesis that Nrf2 and Gfer expression may be involved in the initial hits contributing to the multistep process of colon carcinogenesis. Further larger studies are needed to confirm if Nrf2 and Gfer are potential risk/prognostic factors for cancer development.

      Keywords

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