LGR5 promotes hepatocellular carcinoma metastasis through inducting epithelial-mesenchymal transition

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// Jie Liu 1, 2, * , Guo-Zheng Yu 3, * , Xiao-Ke Cheng 4, * , Xiao-Dong Li 4, 5 , Xian-Tao Zeng 6 and Xue-Qun Ren 1, 4 1 Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China 2 Nursing Department, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China 3 Department of General Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi 435000, Hubei Province, China 4 Center for Evidence-Based Medicine, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China 5 Department of Urology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China 6 Center for Evidence-Based and Translation Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China * These authors have contributed equally to this work Correspondence to: Xue-Qun Ren, email: renxuequn001@163.com Keywords: hepatocellular carcinoma, LGR5, leucine-rich repeat-containing G-protein coupled receptor 5, metastasis, epithelial-mesenchymal transition Received: December 01, 2016 Accepted: January 06, 2017 Published: February 07, 2017 ABSTRACT The purpose of the present study was to investigate the prognostic value of Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) in hepatocellular carcinoma (HCC) and its role in promoting HCC metastasis. The expression level of LGR5 in liver tumor tissues and adjacent non-tumor tissues were detected adopting immunohistochemistry (IHC), real-time PCR (RT-PCR) and western blot assays. Chi-square test was used to evaluate the correlation between LGR5 expression and clinicopathological characteristics. In addition, we assessed the relationship between LGR5 and two epithelial-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) in HCC tissues and cell lines. Our results showed that the expression of LGR5 was significantly higher in liver tumor tissues than in adjacent non-tumor tissues. Moreover, up-regulated LGR5 was associated with larger tumor diameter (>5cm, P=0.001), higher TNM stage (P=0.021), increased recurrence (P=0.023) and growing metastasis (P=0.030). Besides, we found that the expression level of LGR5 was correlated with E-cadherin and N-cadherin. In conclusion, up-regulated LGR5 in HCC patients is associated with malignant clinicopathological characteristics. LGR5 may promote HCC metastasis through inducting EMT process, and thus can be regarded as a candidate biomarker for prognosis and as a target in therapy.