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

Abstract

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.

Keywords

• Bevacizumab
• CXCL16
• non‐small cell lung cancer
• VEGF