Review Article

Can Serum Glypican-3 Be a Biomarker for Effective Diagnosis of Hepatocellular Carcinoma? A Meta-Analysis of the Literature

Table 1

Characteristic and methodology assessment of the included studies.

First author, year, countryCharacteristics of HCCCharacteristics of controlsGPC3
Assay typeCut-off value Antibody for detectionHCC value (ng/mL)Controls value (ng/mL)

Yu [10], 2014, ChinaNALC or hepatitis patients; healthy individualsChemiluminescent immunoassay30 ng/mLGPC3 8G6 mcAb and 7D11 mcAb (Millipore Corporation)108.67 ± 230.043.99 ± 7.68

Lee [11], 2014, Korea62.5% were HBV associatedCLD (HCV) patients; 50% had liver cirrhosisELISA73 ng/mLELISA kit (Wuhan Cusabio Biotech)75.8 ± 117.566.4 ± 33.2

Badr [12], 2014, EgyptNALC (HCV) patientsELISA240 ng/mLELISA kit (Wuhan Uscn)551.47 ± 185.2598.23 ± 73.54

Li [13], 2013, ChinaHBV associated HCCHealthy individualsELISANAELISA kit (usabio Biotech)12.63 ± 2.93 for patients with AFP <400 µg/L; 
20.20 ± 5.41 for patients with AFP ≥ 400 µg/L
1.92 ± 0.95

Chen [14], 2013, ChinaNALC or hepatitis patients; healthy individualsELISA25.25 ng/mL7C8 and GP9 mcAb (self-made)99.94 ± 267.219.44 ± 50.88 for LC patients; 
10.45 ± 46.02 for chronic hepatitis; 4.14 ± 31.65 for 
healthy controls

Abdelgawad [15], 2013, Egypt67.5% were HCV associated; 17.5% were HBV associatedLC patients; healthy individualsELISA4.9 ng/mLELISA kit (Wuhan Uscn) 7.73.24

Gomaa [16], 2012, Egypt12.9% were HBV associated; 87.1% were HCV associatedLC patients with HCV/HBVELISA5.41 ng/mLELISA kit 
(BioMosaics)
8.13 ± 3.253.14 ± 1.16

Wang [17], 2012, ChinaHBV associatedLC patients with HBV ELISANAELISA kit 
(Wuhan Huamei)
NANA

Qiao [18], 2011, China76.2% were HBV associated; 7.9% were HCV associatedLC (HBV/HCV) or hepatitis patients; healthy individualsELISA26.8 ng/mLELISA kit 
(USCN life science)
29.29 ± 17.3412.09 ± 9.69 for LC patients; 9.98 ± 9.60 for chronic hepatitis patients; 5.93 ± 5.46 for healthy controls

Abd El Moety [19], 2011, EgyptHCV associatedLC or hepatitis patients; healthy individualsELISA2.0 ng/mLELISA kit 
(BioMosaics)
34.63 ± 23.8NA

Zhang [20], 2010, ChinaNALC or hepatitis patients with HCV/HBV; healthy individualsImmunoassay3.10 ng/mLSelf-made116.8 ± 98.624.60 ± 24.01 for LC patients; 6.73 ± 12.2 for hepatitis B patients; 13.67 ± 15.68 for hepatitis C patients; 0.86 ± 1.12 
for healthy controls

Youssef [21], 2010, Egypt HCV and HBV associatedLC patients with HBV/HCV;
healthy individuals
ELISA4.6 ng/mLELISA kit 
(BioMosaics)
NANA

Liu [22], 2010, China84% were HBV associated; 16% were HCV associatedLC patients with HBV/HCVELISA300 ng/LELISA kit
(BioMosaics)
NANA

Tangkijvanich [23], 2010, Thailand59% were HBV associated; 11% were HCV associatedLC or hepatitis patients with HBV/HCVELISANASelf-made46.3 (0–7826.6)0 (0–43.6)

Beale [24], 2008, UK60% had ALD and 40% patients had NAFLDLC patients with ALD/NAFLDELISANAELISA kit
(BioMosaics)
161.41 ± 422.33125.41 ± 281.05

Yoshitaka Hippo [25], 2004, JapanNALC patientsELISA2.0 ng/mLSelf-made4.84 ± 8.911.09 ± 0.74

Nakatsura [26], 2003, Japan12.1% were HBV associated; 40.9% were HCV associatedLC patients with HBV/HCV/PBC/AIHELISA10 U/mLSelf-madeNANA

Capurro [27], 2003, Canada44.1% were HBV associated; 27.2% were HCV associated; 14.7% had ALDLC or hepatitis patients with HBV/HCVELISA117 ng/mLSelf-made 
1G12 antibody
NANA

Wang [28], 2014, China84.5% were HBV associated; 9.5% were HBV associated; 3.5% were alcoholic cirrhosis associated LC or hepatitis (HBV) patients; healthy individualsELISANA*ELISA kit (usabio Biotech)4.55 ± 3.59.03 ± 4.1 for LC patients; 4.56 ± 3.2 for HBV chronic hepatitis patients; 6.71 ± 1.8 for healthy controls

Nault [29], 2013, FranceWith alcoholic cirrhotic, 46.4% were early stageAlcoholic cirrhotic patientsELISANA*ELISA kit (Wuhan Cusabio Biotech)1.4 ± 0.5 (early stage)  
4.2 ± 1.8 (advanced stage)
2.5 ± 1.4

Özkan [30], 2011, Turkey52% were HBV associated; 23% were HCV associatedLC patients with HBV/HCV/HDV/AIH/Wilson disease/Cryptogenic liver disease; healthy individuals ELISANA*ELISA kit
(Wuhan EIAab)
5.13 ± 22.75.51 ± 59.2

Yasuda [31], 2010, Japan16% were HBV associated; 77.5% were HCV associatedCLD patients with HBV/HCVELISANA*ELISA kit 
(BioMosaics)
924.8 (495.2, 1335.6)1161.6 (762.0, 1784.0)

NA: data are not available; HBV: hepatitis B virus; HCV: hepatitis C virus; LC: liver cirrhosis; CLD: chronic liver disease; ALD: alcoholic liver disease; ALC: alcoholic liver cirrhosis; NAFLD: nonalcoholic fatty liver diseases; PBC: primary biliary cirrhosis; AIH: autoimmune hepatitis; mean median (25% and 75% quartiles); mean median (ranges); *cutoff values were not provided because these studies found serum GPC3 has no correlation with HCC.