title: SCHLAFEN 5 expression correlates with intestinal metaplasia that progresses to gastric cancer.
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.
  
  
  CONCLUSIONS
  In this study population, elevated SLFN5 protein expression in patients with IM correlated with progression to GC.
authors.affiliation: Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (IDIBELL), Gran Via del Hospitalet 199-203, 08908, Barcelona, Spain.
authors.forename: Osmel
authors.initials: O
authors.lastname: Companioni Nápoles
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Tsao
authors.affiliation: Department of Medicine and Medical Specialities, University of Alcalá, Alcalá de Henares, Community of Madrid, Spain.|Department of Pathology, Hospital Universitario Príncipe de Asturias, Carretera Alcalá-Meco, s/n, 28805, Alcalá De Henares, Community of Madrid, Spain.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Sanz-Anquela
authors.affiliation: Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (IDIBELL), Gran Via del Hospitalet 199-203, 08908, Barcelona, Spain.|Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), Gran Via del Hospitalet 199-203, 08908, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Sala
authors.affiliation: Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (IDIBELL), Gran Via del Hospitalet 199-203, 08908, Barcelona, Spain.
authors.forename: Catalina
authors.initials: C
authors.lastname: Bonet
authors.affiliation: Complejo Hospitalario de Soria, Carretera Logroño 8, 42005, Soria, Spain.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Pardo
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Ornella
authors.initials: O
authors.lastname: Simo
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Milena
authors.initials: M
authors.lastname: Saqui-Salces
authors.affiliation: Department of Histopathology, Hospital Universitario Gregorio Marañón, Calle del Dr. Esquerdo, 46, 28007, Madrid, Spain.
authors.forename: Verónica Parra
authors.initials: VP
authors.lastname: Blanco
authors.affiliation: Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (IDIBELL), Gran Via del Hospitalet 199-203, 08908, Barcelona, Spain.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Gonzalez
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA. merchanj@med.umich.edu.|Department of Internal Medicine, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA. merchanj@med.umich.edu.
authors.forename: Juanita L
authors.identifier: http://orcid.org/0000-0002-0712-1767
authors.initials: JL
authors.lastname: Merchant
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000008:administration & dosage*; D007422:Intestines / Q000473:pathology*; D019169:Jurkat Cells; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; D016898:Interferon-alpha; D012333:RNA, Messenger; C554861:SLFN5 protein, human
keywords: Biomarker; Immunohistochemistry; Intestinal metaplasia; ROC curve; SLFN5