Diagnostic accuracy and prognostic significance of Glypican-3 in hepatocellular carcinoma: A systematic review and meta-analysis

Abstract

PurposeGlypican-3 (GPC-3) expression is abnormal in the occurrence and development of hepatocellular carcinoma (HCC). To explore whether GPC-3 has diagnostic accuracy and prognostic significance of HCC, we did a systematic review and meta-analysis.MethodPubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure were searched with keywords “GPC-3” and “HCC” and their MeSH terms from inception to July 2022. We applied the hierarchical summary receiver operating characteristic model and evaluated the diagnostic value of GPC-3 alone and combination, and the correlation between high and low GPC-3 expression on clinicopathological features and survival data in prognosis.ResultsForty-one original publications with 6,305 participants were included, with 25 of them providing data for diagnostic value and 18 records were eligible for providing prognostic value of GPC-3. GPC-3 alone got good diagnostic value in patients with HCC when compared with healthy control and moderate diagnostic value when compared with patients with cirrhosis. In addition, combination of GPC-3 + AFP and GPC-3 + GP73 got great diagnostic value in HCC versus cirrhosis groups; the combination of GPC-3 can also improve the diagnostic accuracy of biomarkers. Moreover, we discovered that overexpression of GPC-3 was more likely found in HBV infection, late tumor stage, and microvascular invasion groups and causes shorter overall survival and disease free survival, which means poor prognosis.ConclusionGCP-3 could be used as a biomarker in HCC diagnosis and prognosis, especially in evaluated diagnostic value in combination with AFP or GP73, and in forecasting worse survival data of overexpression GPC-3Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42022351566].

Glypicans, 35 years later

“…106 GPC3 can also be found in the serum of a significant proportion of HCC patients (50%-60%), 97,107 and it has been proposed that a GPC3 serum test could be combined with the measurement of serum alpha-fetoprotein (AFP) to increase the sensitivity of early HCC detection. 98,108 In addition, the GPC3 serum test could be used for HCC prognosis, since high GPC3 levels correlate with reduced overall survival. 109,110 In addition to being a diagnostic marker for HCC, GPC3 plays a role in the progression of this malignancy by stimulating canonical Wnt signaling.…”