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.
Bibliographical noteFunding Information:
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 Econom??a 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).
- Intestinal metaplasia
- ROC curve