The clinical significance of CXCL16 in the treatment of advanced non-small cell lung cancer

Abstract

Background: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF)-A, has shown efficacy in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). There are no identified or clinically validated biomarkers to determine the efficacy of bevacizumab. In this study, we assessed the adequacy of chemokine (C-X-C motif) ligand 16 (CXCL16) as a biomarker for patients treated with bevacizumab-containing chemotherapy regimen. Methods: Patients diagnosed histologically with NSCLC were enrolled. Serial serum CXCL16 levels during treatment were measured by enzyme-linked immunosorbent assay. The relationship between serum CXCL16 levels before and after treatment, progression-free survival, and overall survival were analyzed. CXCL16 and VEGF-A expressions in lung cancer tissue were also evaluated by immunohistochemical tests. Results: The median serum level of CXCL16 in these patients was 3.4 ng/mL, which was significantly higher than that in age-matched healthy adults (2.2 ng/mL). Immunohistochemistry results showed that CXCL16 was predominantly localized in the tumor stroma, whereas VEGF was expressed in tumor cells. Including bevacizumab with chemotherapy led to lower CXCL16 levels post-chemotherapy, which correlated with better response rates. In addition, evaluation of differences in serum CXCL16 levels before and after the first-line chemotherapy showed that longer overall survival was achieved in patients who showed a larger decrease in serum CXCL16 levels. Conclusions: According to our findings, serum CXCL16 level was identified as a potential biomarker for the efficacy of therapy, including anti-VEGF. Key points: Significant findings of the study. Patients with NSCLC whose serum CXCL16 levels decreased below 0.07 ng/mL after chemotherapy, showed longer overall survival than those without this decrease. Moreover, low CXCL16 levels corresponded to better response rates among patients with advanced NSCLC treated with bevacizumab-containing chemotherapy. What this study adds. Previously there were no identifiable predictive biomarkers to determine the efficacy of bevacizumab. Data from our findings identified serum CXCL16 level as a potential biomarker for the efficacy of bevacizumab-containing chemotherapy.