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SCHLAFEN 5 expression correlates with intestinal metaplasia that progresses to gastric cancer

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Abstract

Background

Intestinal metaplasia (IM) is a gastric cancer precursor lesion (GCPL) and an extremely high risk factor for progression to gastric cancer (GC). Clinical guidelines recommend that patients with extensive IM undergo a gastroscopy every 3 years. However, protein biomarkers that indicate a transition from IM to GC are lacking. Our group recently identified an interferon-alpha (IFNα)-responsive gene, Schlafen 4 (Slfn4), in immune cells that correlates with metaplastic changes in Helicobacter-infected mice. We therefore tested the hypothesis that a human homolog of Slfn4, namely, Schlafen 5 (SLFN5), correlates with progression of GCPL to GC.

Methods

Jurkat T-lymphoid and HL-60 myeloid cell lines were treated with IFNα, and SLFN5 mRNA was quantified by quantitative PCR. SLFN5 protein expression in the inflamed gastric mucosa was co-localized to specific immune cell types by immunohistochemistry using CD20, CD2, and MAC2 antibodies. SLFN5 expression was also determined by immunohistochemistry in formalin-fixed paraffin-embedded samples from individuals with non-atrophic gastritis, atrophic gastritis, complete IM, incomplete IM, and GC, respectively.

Results

The IFNα treatment of Jurkat and HL-60 cells induced SLFN5 mRNA. SLFN5 protein was expressed mainly by T lymphocytes in inflamed gastric mucosa. The highest level of SLFN5 expression was observed in patients with IM that progressed to GC. Receiver operating characteristic curves demonstrated that correlating SLFN5 expression with the histologic diagnosis of IM significantly increased the probability of identifying patients who may progress to GC.

Conclusion

In this study population, elevated SLFN5 protein expression in patients with IM correlated with progression to GC.

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Abbreviations

CIM:

Complete intestinal metaplasia

GC:

Gastric cancer

IM:

Intestinal metaplasia

CIM → GC:

Complete intestinal metaplasia that progresses to gastric cancer

CIM → Not GC:

Complete intestinal metaplasia that does not progress to gastric cancer

IIM:

Incomplete intestinal metaplasia

IIM → GC:

Incomplete intestinal metaplasia that progresses to gastric cancer

IIM → Not GC:

Incomplete intestinal metaplasia that does not progress to gastric cancer

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Acknowledgments

The authors acknowledge technical contribution from Mrs. Nadia Garcia from the Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology. Sources of funding are the National Institutes of Health P01 DK062041 (JLM); Health Research Funds (Grant Number FIS Exp030077); Grant Sponsor RETICC, Spanish Ministry of Health (Grant Numbers DR06/0020-0015, RD12/0036/0018 and PI10/01089); Instituto de Salud Carlos III, Ministerio de Economía y Competitividad. This study was co-funded by FEDER funds/European Regional Development Fund (ERDF). Osmel Companioni was supported by a PhD fellowship from the Research Institute of Bellvitge (IDIBELL).

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Authors and Affiliations

  1. Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (IDIBELL), Gran Via del Hospitalet 199-203, 08908, Barcelona, Spain

    Osmel Companioni Nápoles, Núria Sala, Catalina Bonet & Carlos A. Gonzalez

  2. Department of Molecular and Integrative Physiology, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA

    Amy C. Tsao, Lin Ding, Ornella Simo, Milena Saqui-Salces & Juanita L. Merchant

  3. Department of Internal Medicine, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA

    Juanita L. Merchant

  4. Department of Medicine and Medical Specialities, University of Alcalá, Alcalá de Henares, Community of Madrid, Spain

    José Miguel Sanz-Anquela

  5. Department of Pathology, Hospital Universitario Príncipe de Asturias, Carretera Alcalá-Meco, s/n, 28805, Alcalá De Henares, Community of Madrid, Spain

    José Miguel Sanz-Anquela

  6. Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), Gran Via del Hospitalet 199-203, 08908, Barcelona, Spain

    Núria Sala

  7. Complejo Hospitalario de Soria, Carretera Logroño 8, 42005, Soria, Spain

    María Luisa Pardo

  8. Department of Histopathology, Hospital Universitario Gregorio Marañón, Calle del Dr. Esquerdo, 46, 28007, Madrid, Spain

    Verónica Parra Blanco

Authors
  1. Osmel Companioni Nápoles
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  2. Amy C. Tsao
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  3. José Miguel Sanz-Anquela
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  4. Núria Sala
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  5. Catalina Bonet
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  6. María Luisa Pardo
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  7. Lin Ding
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  8. Ornella Simo
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  9. Milena Saqui-Salces
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  10. Verónica Parra Blanco
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  11. Carlos A. Gonzalez
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  12. Juanita L. Merchant
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Corresponding author

Correspondence to Juanita L. Merchant.

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The authors declare that they have no conflict of interest with respect to this work.

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Companioni Nápoles, O., Tsao, A.C., Sanz-Anquela, J.M. et al. SCHLAFEN 5 expression correlates with intestinal metaplasia that progresses to gastric cancer. J Gastroenterol 52, 39–49 (2017). https://doi.org/10.1007/s00535-016-1202-4

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  • DOI: https://doi.org/10.1007/s00535-016-1202-4

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