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Open Access Research article

Chemokine receptor CXCR4 expression in hepatocellular carcinoma patients increases the risk of bone metastases and poor survival

Zuo-lin Xiang1, Zhao-chong Zeng1*, Zhao-you Tang2, Jia Fan2, Peng-yuan Zhuang2, Ying Liang2, Yun-shan Tan3 and Jian He1

Author Affiliations

1 Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, PR China

2 Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, PR China

3 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, PR China

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BMC Cancer 2009, 9:176  doi:10.1186/1471-2407-9-176

Published: 9 June 2009

Abstract

Background

The chemokine and bone marrow-homing receptor CXCR4 is implicated in metastases of various cancers. This study was conducted to analyze the association of CXCR4 expression with hepatocellular carcinoma (HCC) bone metastasis and patient survival.

Methods

Tumor tissue from HCC patients with (n = 43) and without (n = 138) bone metastasis was subjected to immunohistochemical staining for CXCR4 using tissue microarrays. Immunoreactivity was evaluated semi-quantitatively. A receiver-operating characteristic-based approach and logistical regression analysis were used to determine the predictive value of clinicopathologic factors, including CXCR4 expression, in bone metastasis. Patient survival was analyzed by Kaplan-Meier curves and log-rank tests.

Results

CXCR4 overexpression was detected in 34 of 43 (79.1%) patients with bone metastases and in 57 of 138 (41.3%) without bone metastases. CXCR4 expression correlated with (correlation coefficient: 0.551, P < 0.001) and was predictive of HCC bone metastases (AUC: 0.689; 95%CI: 0.601 – 0.776; P < 0.001). CXCR4 staining intensity correlated with the bone metastasis-free survival (correlation coefficient: -0.359; P = 0.018). CXCR4 overexpression in primary tumors (n = 91) decreased overall median survival (18.0 months vs. 36.0 months, P <0.001). Multivariable analysis identified CXCR4 as a strong, independent risk factor for reduced disease-free survival (relative risk [RR]: 5.440; P = 0.023) and overall survival (RR: 7.082; P = 0.001).

Conclusion

CXCR4 expression in primary HCCs may be an independent risk factor for bone metastasis and may be associated with poor clinical outcome.