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. 2014 Mar;8(2):177-85.
doi: 10.5009/gnl.2014.8.2.177. Epub 2013 Dec 24.

Clinical utility of plasma glypican-3 and osteopontin as biomarkers of hepatocellular carcinoma

Hyun Jung Lee  1 , Jong Eun Yeon  1 , Sang Jun Suh  1 , Sun Jae Lee  1 , Eileen L Yoon  1 , Keunhee Kang  1 , Yang Jae Yoo  1 , Ji Hoon Kim  1 , Yeon Seok Seo  1 , Hyung Joon Yim  1 , Kwan Soo Byun  1
Affiliations

Clinical utility of plasma glypican-3 and osteopontin as biomarkers of hepatocellular carcinoma

Hyun Jung Lee et al. Gut Liver. 2014 Mar.

Abstract

Background/aims: α-Fetoprotein (AFP) is the biomarker most widely used to detect hepatocellular carcinoma (HCC), despite its suboptimal diagnostic accuracy. Glypican-3 (GPC3) and osteopontin (OPN) are secreted glycoproteins that are reportedly associated with tumorigenesis and metastasis. This study was conducted to evaluate the clinical utility of using plasma GPC3 and OPN as diagnostic biomarkers for HCC.

Methods: We measured the plasma levels of GPC3 and OPN in 120 HCC and 40 chronic liver disease (CLD) patients via an enzyme-linked immunosorbent assay. The diagnostic accuracy of each tumor marker was evaluated using receiver operating characteristic (ROC) curve analysis.

Results: The GPC3 levels in the HCC patients (75.8 ng/mL) were significantly higher (p=0.020) than the levels in patients with CLD (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 patients with low serum AFP and PIVKA II levels, the AUROC of GPC3 remained relatively high (0.66), and GPC3 showed a high sensitivity (62.1%) for detecting small HCC tumors.

Conclusions: The plasma levels of GPC3 and OPN demonstrated low diagnostic accuracy for HCC. However, GPC3 may have a complementary role in diagnosing HCC in patients with nondiagnostic levels of conventional tumor markers and with small-sized tumors.

Keywords: Glypican-3; Hepatocellular carcinoma; Osteopontin.

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Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
(A) Plasma levels of glypican-3 (GPC3) and (B) osteopontin (OPN) in patients with hepatocellular carcinoma (HCC) or chronic liver disease (CLD). The box indicates the 25th and 75th percentile values, and the line indicates the median level, whereas the interquartile range (IQR) extends outside the box. The points outside the IQR are outliers. The plasma GPC3 levels were higher in patients with HCC (75.8 ng/mL) than in patients with CLD (66.4 ng/mL, p=0.020). However, we found no difference in plasma OPN levels based on study group (345.2 ng/mL vs 306.8 ng/mL, p=0.821).
Fig. 2
Fig. 2
Area under the receiver-operating curve (AUROC) for glypican-3 (GPC3), osteopontin (OPN), α-fetoprotein (AFP), and prothrombin-induced vitamin K absence II (PIVKA II). The AUROC was 0.62 for GPC3, 0.51 for OPN, 0.83 for AFP, and 0.80 for PIVKA II, respectively.
Fig. 3
Fig. 3
Area under the receiver-operating curve for glypican-3 (GPC3) and osteopontin (OPN) for chronic liver disease and hepatocellular carcinoma patients with low α-fetoprotein and protein-induced vitamin K absence II levels (0.66 vs 0.23).
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