Prognostic impact of CXCL16 and CXCR6 in non-small cell lung cancer: combined high CXCL16 expression in tumor stroma and cancer cells yields improved survival

BMC Cancer

Research Article

Marte Eilertsen¹  Sigurd M. Hald¹  Roy M. Bremnes²  Sigve Andersen²  Tom Donnem²  Charles Johannessen³  Lill-Tove Busund⁴  Samer Al-Saad⁴  Elin Richardsen⁴  Khalid Al-Shibli⁵  Yury Kiselev⁶  Thomas K. Kilvaer⁷ 

[1] Department of Clinical Medicine, UiT The Arctic University of Norway, 9037, Tromso, Norway;Department of Clinical Medicine, UiT The Arctic University of Norway, 9037, Tromso, Norway;Department of Oncology, University Hospital of North Norway, Tromso, Norway;Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway;Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway;Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway;Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway;Department of Pathology, Nordland Hospital, Bodo, Norway;Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway;Department of Pharmacy, UiT The Arctic University of Norway, Tromso, Norway;Department of Oncology, University Hospital of North Norway, Tromso, Norway;

关键词: NSCLC Cell;    CXCR6 Expression;    NSCLC Cell Line;    NSCLC Tissue;    CXCL16 Expression;   

DOI  :  10.1186/s12885-015-1446-z

 received in 2014-08-05, accepted in 2015-05-19,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe chemokine CXCL16 and its receptor CXCR6 are expressed by a variety of immune cells and have been shown to influence angiogenesis. The expression of CXCR6 and CXCL16 has been examined in numerous human cancers; however no studies have yet investigated their influence on prognosis in non-small cell lung cancer (NSCLC). We aimed to explore their prognostic significance in NSCLC, in addition to examining associations with previously investigated markers.MethodsResected tumor tissue from 335 consecutive unselected stage I-IIIA NSCLC patients (1990–2005) were collected. Immunohistochemistry was used to evaluate the expression of CXCR6 and CXCL16 on tissue microarrays. In vitro, NSCLC cells (NCI-H460, A549 cells) were transfected with CXCL16 siRNA to examine effects on proliferation.ResultsIn univariate analysis, ↑ stromal cell CXCL16 expression was a significant positive prognostic factor (P = 0.016). CXCR6 was expressed in cancer cells, but did not show any prognostic impact. In the multivariate analysis, combined ↑cancer, and ↑stromal cell CXCL16 expression was an independent positive prognostic factor when compared to ↓stromal and ↓cancer cell expression (HR: 0.42; 95 % CI: 0.20–0.88; P = 0.022). Knockdown of CXCL16 by siRNA resulted in accelerated proliferation of NSCLC cell lines.ConclusionWe have shown that combined ↑cancer and ↑stromal cell CXCL16 expression is an independent positive prognostic factor in NSCLC. Further studies are warranted to elucidate the biological mechanism underlying this finding.

【 授权许可】

CC BY   
© Hald et al.; licensee BioMed Central. 2015