Loss of β-arrestin-2 and Activation of CXCR2 Correlate with Lymph Node Metastasis in Non-small Cell Lung Cancer

Background: Although β-arrestin-2 (β-arr2) and CXCR2 have been shown to affect various malignant tumors, their exact roles in lung cancer remain unclear.We investigated expression of β-arr2 and CXCR2 in patients with non-small cell lung cancer (NSCLC) and their correlation with lymph node metastasis and prognosis.Methods: We reviewed medical records of 136 patients with NSCLC who underwent surgical resection, and assessed their specimens immunohistochemically for expression of β-arr2 and CXCR2 in primary tumors and metastatic lymph nodes (MLNs), respectively.Results: High β-arr2 expression was seen in 63 specimens (46.3%), and was significantly associated with male patients (P=0.011),squamous cell carcinoma (P=0.003), and lymph node metastasis (P<0.001).High CXCR2 expression was seen in 62 specimens (45.6%), and was significantly correlated only with lymph node metastasis (P<0.001).Expression of β-arr2 was significantly lower at MLNs than at primary lesions (Z=-2.315;P=0.021; Wilcoxon signed-rank), whereas CXCR2 expression was significantly higher in MLNs than in primary lesions (Z=-3.712;P<0.001; Wilcoxon signed-rank).No relationship was seen between β-arr2 and CXCR2 expression in primary lesions (r=-0.065,P=0.548; Spearman rank coefficient), but they were inversely related in MLNs (r=-0.263,P=0.012).Kaplan-Meier survival curve was shown that low β-arr2 and high CXCR2 expressions was associated with poor survival (log-rank: χ 2 =5.926,P=0.015).Conclusions: β-arr2 may promote lymph node metastasis in NSCLC by modulating CXCR2 activation.