1. Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, #324 Jingwu Road, Jinan 250021, P.R.China;
2. Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center of Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, 200030, China;
3. Department of Oncology, Shanghai Medicine College, Fudan University, Shanghai, 200030, China.
* Lei Cong and Zhi-yong Qiu contributed equally to this work.
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: χ2=5.926, P=0.015).
Conclusions: β-arr2 may promote lymph node metastasis in NSCLC by modulating CXCR2 activation.
Keywords: non-small cell lung cancer, β-arrestin-2, CXCR2, immunohistochemistry.