The prognostic significance of CXCL16 and its receptor C-X-C chemokine receptor 6 in prostate cancer.
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.
Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromsø, Norway. Electronic address: elin-ri@live.no.
Elin
E
Richardsen
Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
Nora
N
Ness
Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
Christian
C
Melbø-Jørgensen
Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
Charles
C
Johannesen
Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
Thea
T
Grindstad
Department of Clinical Pathology, University Hospital of North Norway, Tromsø, Norway.
Cecilie
C
Nordbakken
Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromsø, Norway.
Samer
S
Al-Saad
Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Department of Oncology, University Hospital of North Norway, Tromsø, Norway.
Sigve
S
Andersen
Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Department of Oncology, University Hospital of North Norway, Tromsø, Norway.
Tom
T
Dønnem
Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Department of Urology, University Hospital of North Norway, Tromsø, Norway.
Yngve
Y
Nordby
Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Department of Oncology, University Hospital of North Norway, Tromsø, Norway.
Roy M
RM
Bremnes
Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromsø, Norway.
Lill-Tove
LT
Busund
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*
C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus