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
AuthorHald, Sigurd; Kiselev, Yury; Al-Saad, Samer; Richardsen, Elin; Johannessen, Charles; Eilertsen, Marte; Kilvær, Thomas Karsten; Al-Shibli, Khalid; Andersen, Sigve; Busund, Lill-Tove; Bremnes, Roy M.; Dønnem, Tom
Methods: Resected 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.
Results: In 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.
Conclusion: We 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.