Significance of CXCR4, phosphorylated STAT3 and VEGF-A expression in resected non-small cell lung cancer

Abstract

C-X-C chemokine receptor type 4 (CXCR4) plays an important role in determining the metastatic potential of non-small cell lung cancer. In order to elucidate the effect and mechanism of CXCR4 in tumor angiogenesis we evaluated the clinical significance of CXCR4, phosphorylated signal transducer and activator of transcription 3 (P-STAT3), and vascular endothelial growth factor (VEGF) expression in patients with completely resected non-small cell lung cancer (NSCLC). A total of 208 cases of resected NSCLC were collected, and expression of CXCR4, P-STAT3 and VEGF-A in tumor tissue was investigated using immunohistochemistry (IHC). We reviewed the patient clinical records to determine the association of the expression of these proteins with the clinical course of the disease. Expression of CXCR4, P-STAT3 and VEGF-A was detected in 56.3, 46.2 and 51.9% of the samples, respectively. We observed co-expression between CXCR4, P-STAT3 and VEGF-A. Using multivariate analysis, the expression levels of CXCR4 and VEGF-A were identified as independent prognostic factors that affected overall survival. In conclusion, the results of this study suggest that CXCR4, P-STAT3 and VEGF-A expression may play a role in tumor progression and angiogenesis of NSCLC. However, further studies are needed to uncover the detailed mechanism that underlies the role of these proteins in NSCLC.

Figure 1.

Immunohistochemical expression of (A and B) CXCR4, (C) P-STAT3 and (D) VEGF-A protein in NSCLC tissues (SP method, x200). (A) Immunoreactivity was observed in the cytoplasm of the malignant cells. Brown granules in the cytoplasm of the NSCLC cells indicate CXCR4 protein. (B) Nuclear staining of CXCR4 protein in the NSCLC tissues, and (C) nuclear staining of P-STAT3 protein in the NSCLC tissues. (D) Brown granules in the cytoplasm of the NSCLC cells indicate VEGF-A expression.

Figure 2.

Overall survival curves for patients with resected NSCLC according to the expression levels of CXCR4, P-STAT3 and VEGF-A. (A) The overall survival time of patients with CXCR4-positive cancers was significantly lower compared with the survival time of patients with CXCR4-negative cancers (P<0.05). (B) The overall survival time of patients with P-STAT3-positive cancers was significantly lower compared with the survival time of patients with P-STAT3-negative cancers (P<0.05). (C) The overall survival time of patients with VEGF-A-positive cancers was significantly lower compared with the survival time of patients with VEGF-A-negative cancers (P<0.05).