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Toll-like receptors 3, 7, 8, and 9 in gastric cancer
Authors:Maarit Eskuri  Niko Kemi  Olli Helminen  Heikki Huhta  Joonas H. Kauppila
Affiliation:1. Cancer and Translational Medicine Research Unit, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland;2. Surgery Research Unit, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland;3. Surgery Research Unit, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland

Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden

Abstract:Toll-like receptors (TLRs) have been shown to have anti-tumor, pro-tumor, or even dual effects in cancer, and are thus potential prognostic biomarkers and immunotherapeutic targets. The present study aimed to evaluate associations between endosomal TLRs, namely TLR3, TLR7, TLR8, and TLR9, expression and clinicopathological variables and survival in gastric cancer. A total of 564 gastric adenocarcinoma patients were included in this retrospective cohort study. Samples and clinicopathological data were retrieved and organized into tissue microarray blocks. Protein expressions were detected by immunohistochemical staining. The patients were divided into low expression and high expression groups by median values of expression. Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for confounders. Patients with high nuclear TLR3 expression had significantly poorer 5-year survival than the low nuclear TLR3 expression group in the univariable analysis (crude HR 1.31, 95% CI 1.07–1.60). With radically resected patients, poor prognosis was also seen in the multivariable analysis (adjusted HR 1.38, 95% CI 1.08–1.77). Cytoplasmic TLR3, TLR7, TLR8, and TLR9 were not associated with 5-year survival. In conclusion, high nuclear TLR3 expression seems to have prognostic impact in gastric cancer, while TLR7, TLR8, and TLR9 do not.
Keywords:Toll-like receptors  TLR3  TLR7  TLR8  TLR9  gastric cancer
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