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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.

SUBMITTER: Shibata Y

PROVIDER: S-EPMC7180569 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Shibata Yuji Y Kobayashi Nobuaki N Sato Takashi T Nakashima Kentaro K Kaneko Takeshi T

Thoracic cancer 20200312 5

<h4>Background</h4>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.<h4>Methods</h4>Patients dia ...[more]

PMID: 32163231

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Project description:BackgroundAmrubicin chemotherapy is a treatment option for patients with non-small cell lung cancer (NSCLC) after third-line treatment in Japan. Although topoisomerase-II (Topo-II), a target of amrubicin, has been reported to be a prognostic or predictive marker for chemosensitivity and clinical outcomes in various types of malignancies, its effects in the Japanese population remain unknown.MethodsData regarding 44 patients with advanced NSCLC treated with amrubicin between April 2004 and May 2014 were retrospectively analyzed. We evaluated the expression levels of Topo-II by immunohistochemical staining of tumor specimens obtained via biopsy or surgical resection.ResultsThe majority of enrolled patients were men (68%) with a median age of 67 (range, 43-78) years. The most common histological type was adenocarcinoma (70%). High Topo-II expression was observed in 13 (30%) of the 44 patients. The median progression-free survival and overall survival (OS) durations were 1.8 and 8.8 months, respectively. While there was no significant association between Topo-II expression and progression-free survival, patients with low Topo-II expression had significantly longer OS than did those with high Topo-II expression. Good performance status and low expression of Topo-II were all significantly associated with a favorable OS.ConclusionLow expression of Topo-II was identified as an independent prognostic factor for longer survival in patients with NSCLC receiving amrubicin, a Topo-II inhibitor.Key pointsSignificant findings of the study The median progression-free survival and overall survival (OS) durations were 1.8 and 8.8 months, respectively. While there was no significant association between Topo-II expression and progression-free survival, patients with low Topo-II expression had significantly longer OS than did those with high Topo-II expression. Good performance status and low expression of Topo-II were all significantly associated with a favorable OS. What this study adds This study is the first to assess the effects of topoisomerase-II (Topo-II), a target of amrubicin, as a prognostic or predictive marker for chemosensitivity and clinical outcomes in the Japanese population.

Dataset Information

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

Publications

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

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