Abstract
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.
Highlights
The chemokine CXCL16 and its receptor CXCR6 are expressed by a variety of immune cells and have been shown to influence angiogenesis
Western blot We used Western blotting to verify the specificity of the CXCL16 and CXCR6 antibodies (Fig. 1) as described
We present the first study on the prognostic impact of the chemokines CXCL16 and CXCR6 in lung cancer
Summary
The 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; 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. Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer, representing 80–85 % of new cases. Chemokines are associated with tumor progression [5], metastasis [6] and angiogenesis [7], in addition to leukocyte recruitment to the tumor microenvironment [8]. Chemokines have been recognized as targets in cancer therapy as well as potential agents for immunotherapy, Hald et al BMC Cancer (2015) 15:441 reflecting their multifaceted role in the development and progression of cancer [9, 10]
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