Prognostic and clinicopathological significance of glypican-3 overexpression in hepatocellular carcinoma: a meta-analysis

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.