Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 28, 2012; 18(12): 1328-1338
Published online Mar 28, 2012. doi: 10.3748/wjg.v18.i12.1328
Loss of Wnt5a and Ror2 protein in hepatocellular carcinoma associated with poor prognosis
Ming Geng, Yong-Cheng Cao, Ying-Jian Chen, Hui Jiang, Li-Quan Bi, Xiao-Hong Liu
Ming Geng, Yong-Cheng Cao, Hui Jiang, Li-Quan Bi, Xiao-Hong Liu, Department of Pathology, General Hospital of Jinan Military Command, Jinan 250031, Shandong Province, China
Ying-Jian Chen, Department of Laboratory Medicine, General Hospital of Jinan Military Command, Jinan 250031, Shandong Province, China
Author contributions: Geng M and Cao YC contributed equally to this work; Geng M and Cao YC performed the experiments and data analysis; Chen YJ performed the experiments; Jiang H and Bi LQ performed the experiments, collected the samples and the patients information; Geng M, Cao YC and Liu XH contributed to research designation, manuscript preparation and editing.
Supported by The fund of Nature Science Foundation of Shandong Province, No. ZR2009CM041
Correspondence to: Xiao-Hong Liu, MD, PhD, Associate Professor, Department of Pathology, General Hospital of Jinan Military Command, Shifang Road 25, Jinan 250031, Shandong Province, China. liuxh333@126.com
Telephone: +86-531-51666857 Fax: +86-531-51666284
Received: October 5, 2011
Revised: January 18, 2012
Accepted: February 8, 2012
Published online: March 28, 2012

AIM: To investigate the expression and clinical significance of Wnt member 5a (Wnt5a) and receptor tyrosine kinase-like orphan receptor 2 (Ror2) in hepatocellular carcinoma (HCC).

METHODS: HCC tissues obtained from 85 patients were examined the mRNA expression of Ror2 by real-time reverse transcription polymerase chain reaction and the protein expressions of Wnt5a, Ror2, β-catenin and Ki-67 via immunohistochemical staining. The correlation between protein expression and HCC patients’ clinicopathology data and prognoses were analyzed.

RESULTS: Compared to nontumorous (hepatitis or cirrhotic) tissues, Ror2 mRNA expression was clearly decreased in HCC. Ror2 and Wnt5a protein expressions in the majority of HCC patients (63% and 77%, respectively) was significantly less in tumor tissues, as compared to adjacent nontumorous tissues, and this reduction was correlated with increasing serum α-fetoprotein and tumor stage. In 68% (58/85) of the HCC cases, the expression of β-catenin in tumor tissues was either downregulated in the cellular membrane, upregulated in the cytoplasm, or both. Survival analysis indicated that Wnt5a and Ror2 protein expressions could be regarded as independent prognostic factors for HCC; HCC patients with decreased Wnt5a or Ror2 protein expression had a poorer prognosis than those with elevated Wnt5a and Ror2 expression (P = 0.016, P = 0.007, respectively).

CONCLUSION: Wnt5a and Ror2 may serve as tumor suppressor genes in the development of HCC, and may serve as clinicopathologic biomarkers for prognosis in HCC patients.

Keywords: Hepatocellular carcinoma, Wnt5a, Receptor tyrosine kinase-like orphan receptor 2, β-catenin, Prognosis