Elucidation of the Usefulness of Glypican-3, a Hepatocellular Carcinoma Biomarker, with the Fully Automated LUMIPULSE^® System

Abstract

Background: Glypican-3 (GPC3) is expressed in most of hepatocellular carcinoma (HCC) and GPC3 immunohistochemical staining is widely used in the clinical setting, but it has not been recommended as a blood biomarker, mainly due to its heterogeneous nature and the lack of established assay system. Here, we developed and evaluated the basic performance of fully automated GPC3 immunoassay kits which detect the full-length or the N-terminal fragments. We analyzed the molecular forms of GPC3 in HCC serum and evaluated the diagnostic performance of GPC3 and other biomarkers. Methods: We examined the analytical performance of the GPC3 kits. Then, the automated GPC3 assays were compared with an established ELISA kit. Afterwards, we determined the clinical cutoff of GPC3 and compared its diagnostic performance to alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) using 180 serum samples from clinically diagnosed patients. Results: GPC3 assays showed good analytical performance. The level of GPC3 in HCC was higher than recorded in healthy or other liver diseases' sera. The AUC of GPC3 was 0.90, whereas the AUCs of AFP and PIVKA-II were 0.89 and 0.76, respectively. Conclusion: Automated GPC3 assays with stable performance against GPC3 in screening HCC have been established and the diagnostic accuracy of GPC3 was as good as AFP.

Glypicans, 35 years later

“…[101][102][103][104][105] Likewise, the Clinical Practice Guidelines of the European Association for the Study of Liver Disease includes GPC3 as one of the markers to be tested to confirm the presence of HCC. 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.…”

“…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 …”