Meta-Analysis
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World J Gastroenterol. May 28, 2014; 20(20): 6336-6344
Published online May 28, 2014. doi: 10.3748/wjg.v20.i20.6336
Prognostic and clinicopathological significance of glypican-3 overexpression in hepatocellular carcinoma: A meta-analysis
Jia Li, Jian-Zhi Gao, Jing-Li Du, Li-Xin Wei
Jia Li, Jian-Zhi Gao, Jing-Li Du, Li-Xin Wei, Department of Pathology, Chinese PLA General Hospital, Beijing 100853, China
Jia Li, Department of Clinical Medicine, Medical College, Nankai University, Tianjin 300071, China
Jian-Zhi Gao, Department of Basic Medical Sciences, Xinxiang Medical College, Xinxiang 453000, Henan Province, China
Author contributions: Wei LX and Li J designed the study; Li J performed the literature search; Li J, Gao JZ and Du JL extracted data from eligible studies and performed the statistical analysis; Li J wrote the manuscript; and Wei LX was responsible for revising the manuscript.
Correspondence to: Li-Xin Wei, PhD, Department of Pathology, Chinese PLA General Hospital, Haidian District, 28 Fuxing Road, Beijing 100853, China. weilx301@263.net
Telephone: +86-10-66939726 Fax: +86-10-66939726
Received: October 31, 2013
Revised: January 9, 2014
Accepted: January 20, 2014
Published online: May 28, 2014
Abstract

AIM: To investigate the prognostic and clinicopathological significance of glypican-3 (GPC3) overexpression in hepatocellular carcinoma (HCC).

METHODS: Publications were searched using PubMed, EMBASE, the Cochrane Library and the Chinese Biomedical Literature Database up to March 2013. Inclusion and exclusion criteria were established to screen eligible studies for meta-analysis. The hazard ratios (HRs) of the eligible studies were pooled using RevMan 5.2 software to evaluate the impact of GPC3 overexpression on overall survival (OS) and disease-free survival (DFS) in HCC patients. The correlation between GPC3 expression and clinicopathological parameters of HCC was also analyzed.

RESULTS: A total of five studies with 493 patients were included in the meta-analysis. The combined HRs indicated that GPC3 overexpression can predict poor OS (n = 362 in 3 studies, HR = 2.18, 95%CI: 1.47-3.24, Z = 3.86, P = 0.0001) and DFS (n = 325 in 3 studies, HR = 2.05, 95%CI: 1.43-2.93, Z = 3.94, P < 0.0001) in HCC patients without heterogeneity. Egger’s and Begg’s tests were applied to detect publication bias, and the results showed that there was no evidence of publication bias detected in the OS studies (the P value for Egger’s test was 0.216) or DFS studies (the P value for Egger’s test was 0.488). The combined odds ratios (ORs) suggested that GPC3 expression tends to be associated with tumor vascular invasion (OR = 2.74, 95%CI: 1.15-6.52, P = 0.02), hepatic cirrhosis (OR = 2.10, 95%CI: 1.31-3.36, P = 0.002), poor tumor differentiation (OR = 0.22, 95%CI: 0.13-0.40, P < 0.00001) and advanced TNM stage (OR = 0.31, 95%CI: 0.18-0.51, P < 0.00001).

CONCLUSION: From this study, we conclude that GPC3 overexpression tends to be associated with a poor prognosis (poor OS or DFS) in HCC.

Keywords: Hepatocellular carcinoma, Glypican-3, Prognosis, Clinicopathological parameter, Meta-analysis

Core tip: Glypican-3 (GPC3) is known to be a specific and available molecular marker for the diagnosis of hepatocellular carcinoma (HCC). However, the prognostic value of GPC3 overexpression in patients with HCC is less researched and remains controversial. We performed the meta-analysis including six eligible studies and demonstrated that GPC3 overexpression was associated with poor overall survival and disease-free survival in HCC. We also found that GPC3 expression was closely related with tumor vascular invasion, hepatic cirrhosis, tumor grade and tumor stage in HCC.