The prognostic significance of CXCL16 and its receptor C-X-C chemokine receptor 6 in prostate cancer

Abstract

The chemokine CXCL16 and its receptor, C-X-C chemokine receptor (CXCR6), affect tumor progression through different pathways, including leukocyte recruitment and function, cellular senescence, tumor cell proliferation, survival, invasion, and metastasis. We examined how the expression of CXCL16/CXCR6 in prostate cancer (PC) was related to clinicopathological features and activation of inflammatory cells. Tissue microarrays from 535 patients were constructed from tumor epithelial and tumor stromal areas of primary PC. Immunohistochemistry was used to evaluate the expression of CXCL16/CXCR6, CD3(+) T cells (CD4(+), CD8(+)), and CD20(+) B cells. Survival analyses were used to evaluate their prognostic impact. Expression of CXCL16 in PC cell lines (DU145 and PC3) and the effect on proliferation and migration were examined. High expression levels of CXCL16 [hazard ratio (HR), 2.52; 95% CI, 1.12-5.68; P = 0.026] and CXCR6 (HR, 2.29; 95% CI, 1.10-4.82; P = 0.028) were each independent predictors for clinical failure. High co-expression of CXCL16 and CXCR6 (HR, 5.1; 95% CI, 1-15.9; P = 0.05) was associated with negative prognostic factors, such as Gleason grade 4 + 3, Gleason score ≥7, vascular infiltration, and positive surgical margins. As a conclusion, high protein expression of CXCL16 and high protein co-expression of CXCL16/CXCR6 in PC were independent predictors for a worse clinical outcome.