Overexpression of glypican-3 is a predictor of poor prognosis in hepatocellular carcinoma

Abstract

Background:Glypican-3 (GPC3) has been widely recognized in the progression of liver tumors for several years. The relationship between overexpression of GPC3 and the poorer prognosis of patients with hepatocellular carcinoma (HCC) was performed by 2 meta-analyses. However, there were also some latest literatures that indicated different conclusions distinctly. It is necessary for us to carry out a meta-analysis by adding the latest data from current studies to explore the correlation between GPC3 and prognostic value in HCC.Methods:We conducted a meta-analysis including a total of 14 studies to assess the potential prognostic significance of GPC3 expression for overall survival (OS) and disease-free survival (DFS). The expression of GPC3 was assessed by immunohistochemistry.Results:Fourteen studies with 2364 patients were incorporated in the meta-analysis. The combined hazard ratios (HRs) revealed that the overexpression of GPC3 could forecast a poor OS [n = 2233 in 12 studies, HR = 1.40, 95% confidence interval (95% CI): 1.07–1.85, Z = 2.42, P = .02] and DFS (n = 1308 in 10 studies, HR = 1.61, 95% CI: 1.13–2.30, Z = 2.63, P = .008) in HCC patients. Subgroup treated by hepatectomy indicated that the pooled HR of OS was 1.43 (95% CI: 1.01–2.01, P = .04) and the combined HR of DFS was 1.59 (95% CI: 1.09–2.31, P = .02). The pooled odds ratios (ORs) showed that high GPC3 expression was also extensively associated with worse tumor differentiation, later tumor stage, presence of vascular invasion, and hepatitis B virus (HBV) infection. Subgroup analyses for GPC3 on HCC OS based on the studies categorized by regions, follow-up period, and sample size were also conducted.Conclusion:The meta-analysis indicated that overexpression of GPC3 was significantly associated with poor prognosis in patients with HCC.

Glypican-3: A New Target for Diagnosis and Treatment of Hepatocellular Carcinoma

“…The results showed that overexpression of GPC3 may indicate a poor prognosis. The high expression of GPC3 was significantly associated with malignant events such as poor tumor differentiation, advanced stage of tumor, vascular invasion, and HBV infection [66].…”

“…Lots of tissue microarray and immunohistochemical data showed that GPC3 is highly expressed in more than 70% of HCC samples, but not in normal liver tissues, benign liver lesions, liver cirrhosis or hepatitis tissues [5,[63][64][65]. Also, the expression level of GPC3 is correlated with prognosis [66][67][68][69]. In addition, GPC3 is also highly expressed in some other cancers such as hepatoblastoma [70], lung squamous cell carcinoma [71], ovarian yolk sac tumor [72], melanoma [73], and urothelial carcinoma [74].…”

Proteoglycans Are Attractive Biomarkers and Therapeutic Targets in Hepatocellular Carcinoma

“…Many studies have reported that GPC3 expression is correlated with a poor prognosis in HCC [ 38 , 39 ], and that GPC3 may be a prognostic marker for curative resection [ 40 , 41 , 42 ] and HCC recurrence following liver transplantation [ 43 ]. Two meta-analyses recently indicated that GPC3 overexpression was significantly associated with poor prognosis in patients with HCC [ 44 , 45 ].…”

Plasma and tumoral glypican‐3 levels are correlated in patients with hepatitis C virus‐related hepatocellular carcinoma

“…Taken together, these findings suggest that patients with higher plasma GPC3 levels are in more advanced stages of HCC. Indeed, it has been reported that the expression of tumoral GPC3 increases with tumor progression . These results seem to suggest that the cut‐off value of plasma GPC3 levels reflects tumoral GPC3 expression in patients with HCV‐related HCC.…”