Clinical Utility of Plasma Glypican-3 and Osteopontin as Biomarkers of Hepatocellular Carcinoma

Background/Aims: α-Fetoprotein (AFP) is the biomarkermost widely used to detect hepatocellular carcinoma (HCC),despite its suboptimal diagnostic accuracy. Glypican-3 (GPC3)and osteopontin (OPN) are secreted glycoproteins that are reportedlyassociated with tumorigenesis and metastasis. Thisstudy was conducted to evaluate the clinical utility of usingplasma GPC3 and OPN as diagnostic biomarkers for HCC. Methods: We measured the plasma levels of GPC3 and OPNin 120 HCC and 40 chronic liver disease (CLD) patients viaan enzyme-linked immunosorbent assay. The diagnostic accuracyof each tumor marker was evaluated using receiveroperating characteristic (ROC) curve analysis. Results: TheGPC3 levels in the HCC patients (75.8 ng/mL) were significantlyhigher (p=0.020) than the levels in patients withCLD (66.4 ng/mL). The area under the ROC curve (AUROC)values for GPC3 and OPN were 0.62 and 0.51, respectively. In subgroup analyses, including subgroups of HCC patientswith low serum AFP and PIVKA II levels, the AUROC of GPC3remained relatively high (0.66), and GPC3 showed a highsensitivity (62.1%) for detecting small HCC tumors. Conclusions:The plasma levels of GPC3 and OPN demonstratedlow diagnostic accuracy for HCC. However, GPC3 may havea complementary role in diagnosing HCC in patients withnondiagnostic levels of conventional tumor markers and withsmall-sized tumors. (Gut Liver 2014;8:177-185)