J Cancer 2017; 8(14):2785-2792. doi:10.7150/jca.19631

Research Paper

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

Lei Cong1*, Zhi-yong Qiu1*, Yang Zhao2, 3, Wei-bo Wang1, Cai-xia Wang1, Hong-chang Shen1✉, Jun-qing Han1✉

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.

Abstract

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.

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How to cite this article:
Cong L, Qiu Zy, Zhao Y, Wang Wb, Wang Cx, Shen Hc, Han Jq. Loss of β-arrestin-2 and Activation of CXCR2 Correlate with Lymph Node Metastasis in Non-small Cell Lung Cancer. J Cancer 2017; 8(14):2785-2792. doi:10.7150/jca.19631. Available from http://www.jcancer.org/v08p2785.htm