Expression of the Chemokine Receptor CXCR3 Correlates with Dendritic Cell Recruitment and Prognosis in Gastric Cancer

Genet Test Mol Biomarkers. 2018 Jan;22(1):35-42. doi: 10.1089/gtmb.2017.0125. Epub 2017 Dec 21.

Abstract

Aim: The aim of this study was to investigate whether CXCR3 expression is associated with: infiltration of dendritic cells (DCs) and CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs); various clinical features; and overall survival (OS) of patients diagnosed with gastric cancer (GC).

Materials and methods: The study included 169 GC specimens and 91 corresponding paracancerous tissues. Immunohistochemistry was conducted to determine the expression of CXCR3 and the presence of DCs and CD4+ and CD8+ TILs. Statistical analyses were done using SPSS 17.0 software.

Results: CXCR3 expression in GC tissues was significantly higher than in paracancerous tissues (p < 0.001). Higher CXCR3 expression was associated with increased DC and both CD8+ and CD4+ TIL infiltration (p = 0.003, p = 0.008, and p = 0.016, respectively). In contrast, low CXCR3 expression was correlated with greater tumor invasion depth, III/IV TNM stage, lymph node metastasis, and more poorly differentiated tumor cells in GC patients (p = 0.001, p = 0.005, p = 0.037, and p = 0.004, respectively). Univariate analysis indicated that patients with high CXCR3 expression and high DC and CD8+ TIL infiltration had longer OS (log-rank test, p < 0.001, p = 0.018, and p = 0.001, respectively). Univariate and multivariate analyses indicated that CXCR3 expression was an independent prognostic factor for OS (p < 0.001, in both cases).

Conclusion: The results of this study indicate that CXCR3 overexpression in GC is associated with increased DC and TIL infiltration and improved OS, and thus could be further exploited as a biomarker of favorable prognosis and a therapeutic target in GC.

Keywords: CXCR3; biomarker; dendritic cells; gastric cancer; tumor-infiltrating lymphocytes.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, CXCR3 / biosynthesis*
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology
  • Retrospective Studies
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • CXCR3 protein, human
  • Receptors, CXCR3