Retrospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2016; 22(14): 3829-3836
Published online Apr 14, 2016. doi: 10.3748/wjg.v22.i14.3829
Oncogenic Wnt3a expression as an estimable prognostic marker for hepatocellular carcinoma
Liu-Hong Pan, Min Yao, Yin Cai, Juan-Juan Gu, Xu-Li Yang, Li Wang, Deng-Fu Yao
Liu-Hong Pan, Deng-Fu Yao, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Min Yao, Departments of Immunology, Medical College of Nantong University, Nantong 226001, Jiangsu Province, China
Li Wang, Medical Informatics, Medical College of Nantong University, Nantong 226001, Jiangsu Province, China
Yin Cai, Juan-Juan Gu, Xu-Li Yang, Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Author contributions: Pan LH, Yao M contributed equally to this work; Pan LH, Yao M and Wang L designed and performed the research; Cai Y, Gu JJ and Yang XL contributed new reagents/analytic tools; Pan LH and Yao M analyzed the data; Pan LH, Yao M and Yao DF wrote the paper; Yao DF is the guarantor; all authors have read and approved the final version to be published.
Supported by the International S&T Cooperation Program, No. 2013DFA32150 of China.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Deng-Fu Yao, MD, PhD, Professor, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, No. 20 West Temple Road, Nantong 226001, Jiangsu Province, China. yaodf@ahnmc.com
Telephone: +86-513-85052297 Fax: +86- 513-85052523
Received: November 1, 2015
Peer-review started: November 6, 2015
First decision: December 11, 2015
Revised: January 6, 2016
Accepted: January 17, 2016
Article in press: January 18, 2016
Published online: April 14, 2016
Processing time: 145 Days and 3.4 Hours
Abstract

AIM: To investigate member 3a of Wingless-type MMTV integration site family (Wnt3a) expression in cancerous and surrounding tissues and the relationship between clinicopathologic features of hepatocellular carcinoma (HCC) and Wnt3a expression.

METHODS: Wnt3a expression and cellular distribution and clinicopathologic characteristics in cancerous tissue and matched surrounding tissues were analyzed in 80 HCC patients from January 2006 to August 2008 by tissue microarrays and immunohistochemistry. The overall and disease-free survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models.

RESULTS: The incidence of oncogenic Wnt3a expression in the cancerous group was up to 96.25% (77 of 80), which was significantly higher (χ2 = 48.818, P < 0.001) than that in the surrounding group (46.25%, 37 of 80). Brown Wnt3a staining gradually increased with clinical staging that showed very strong staining in advanced HCC. The clinicopathologic features of high Wnt3a expression in HCC were related to poorly-differentiated grade (χ2 = 20.211, P < 0.001), liver cirrhosis (χ2 = 8.467, P < 0.004), hepatitis B virus (HBV) infection (χ2 = 12.957, P < 0.001), higher tumor-node-metastasis stage (χ2 = 22.960, P < 0.001), and 5-year survival rate (χ2 = 15.469, P < 0.001).

CONCLUSION: Oncogenic Wnt3a expression associated with HBV infection and cirrhotic liver might be an independent prognostic factor for HCC.

Keywords: Hepatocellular carcinoma; Prognosis; Wnt3a; Wnt/β-catenin signal; Tissue microarrays; Immunohistochemistry

Core tip: Protein expression of member 3a of Wingless-type MMTV integration site family (Wnt3a) was shown to be increased progressively in hepatocarcinogenesis. Oncogenic Wnt3a expression associated with HBV infection and cirrhotic liver might be an independent prognostic factor for hepatocellular carcinoma (HCC). Survival analysis showed that HCC patients with high Wnt3a expression had a significantly shorter survival time compared with those low or no Wnt3a expression.