Osmel Companioni Nápoles1, Amy C Tsao2, José Miguel Sanz-Anquela3,4, Núria Sala1,5, Catalina Bonet1, María Luisa Pardo6, Lin Ding2, Ornella Simo2, Milena Saqui-Salces2, Verónica Parra Blanco7, Carlos A Gonzalez1, Juanita L Merchant8,9. 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. 2. Department of Molecular and Integrative Physiology, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA. 3. Department of Medicine and Medical Specialities, University of Alcalá, Alcalá de Henares, Community of Madrid, Spain. 4. Department of Pathology, Hospital Universitario Príncipe de Asturias, Carretera Alcalá-Meco, s/n, 28805, Alcalá De Henares, Community of Madrid, Spain. 5. Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), Gran Via del Hospitalet 199-203, 08908, Barcelona, Spain. 6. Complejo Hospitalario de Soria, Carretera Logroño 8, 42005, Soria, Spain. 7. Department of Histopathology, Hospital Universitario Gregorio Marañón, Calle del Dr. Esquerdo, 46, 28007, Madrid, Spain. 8. 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. 9. Department of Internal Medicine, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA. merchanj@med.umich.edu.
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.
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:JurkatT-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.
Authors: Ramon Clèries; Jordi Galvez; Meritxell Espino; Josepa Ribes; Virginia Nunes; Miguel López de Heredia Journal: Comput Biol Med Date: 2012-01-24 Impact factor: 4.589
Authors: Carlos A González; Maria Luisa Pardo; Juan Maria Ruiz Liso; Pablo Alonso; Catalina Bonet; Raul M Garcia; Núria Sala; Gabriel Capella; José Miguel Sanz-Anquela Journal: Int J Cancer Date: 2010-12-01 Impact factor: 7.396
Authors: Efstratios Katsoulidis; Evangelos Mavrommatis; Jennifer Woodard; Mario A Shields; Antonella Sassano; Nathalie Carayol; Konrad T Sawicki; Hidayatullah G Munshi; Leonidas C Platanias Journal: J Biol Chem Date: 2010-10-18 Impact factor: 5.157
Authors: Wendy J van Zuylen; Valerie Garceau; Adi Idris; Kate Schroder; Katharine M Irvine; Jane E Lattin; Dmitry A Ovchinnikov; Andrew C Perkins; Andrew D Cook; John A Hamilton; Paul J Hertzog; Katryn J Stacey; Stuart Kellie; David A Hume; Matthew J Sweet Journal: PLoS One Date: 2011-01-07 Impact factor: 3.240
Authors: Mohamad El-Zaatari; John Y Kao; Art Tessier; Longchuan Bai; Michael M Hayes; Clinton Fontaine; Kathryn A Eaton; Juanita L Merchant Journal: PLoS One Date: 2013-03-08 Impact factor: 3.240
Authors: Lin Ding; Michael M Hayes; Amanda Photenhauer; Kathryn A Eaton; Qian Li; Ramon Ocadiz-Ruiz; Juanita L Merchant Journal: J Clin Invest Date: 2016-07-18 Impact factor: 14.808
Authors: Mariafausta Fischietti; Frank Eckerdt; Gavin T Blyth; Ahmet D Arslan; William M Mati; Chidera V Oku; Ricardo E Perez; Catalina Lee-Chang; Ewa M Kosciuczuk; Diana Saleiro; Elspeth M Beauchamp; Maciej S Lesniak; Daniela Verzella; Leyu Sun; Eleanor N Fish; Guang-Yu Yang; Wenan Qiang; Leonidas C Platanias Journal: Oncogene Date: 2021-04-12 Impact factor: 9.867
Authors: Athanasios Koulis; Natasha Di Costanzo; Catherine Mitchell; Stephen Lade; David Goode; Rita A Busuttil; Alex Boussioutas Journal: BMC Gastroenterol Date: 2022-04-21 Impact factor: 2.847
Authors: Stefan Reich; Chi D L Nguyen; Canan Has; Sascha Steltgens; Himanshu Soni; Cristina Coman; Moritz Freyberg; Anna Bichler; Nicole Seifert; Dominik Conrad; Christiane B Knobbe-Thomsen; Björn Tews; Grischa Toedt; Robert Ahrends; Jan Medenbach Journal: Nat Commun Date: 2020-06-10 Impact factor: 14.919
Authors: A D Arslan; A Sassano; D Saleiro; P Lisowski; E M Kosciuczuk; M Fischietti; F Eckerdt; E N Fish; L C Platanias Journal: Oncogene Date: 2017-07-03 Impact factor: 9.867