Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker.
With the global pandemic of hepatitis B and C infections, the incidence of Hepatocellular carcinoma (HCC) is rapidly increasing world wide. We identified glypican-3 (GPC3), a novel oncofetal gene over-expressed specifically in human HCC, as based on data of cDNA microarrays. As GPC3 is a GPI-anchored membrane protein and could be secreted, we attempted to detect secreted GPC3 protein in sera from HCC patients using Western blotting and ELISA. GPC3 protein was positive in sera of 40.0% (16/40) of HCC patients, and negative in sera from subjects with liver cirrhosis (LC) (0/13), chronic hepatitis (CH) (0/34), and healthy donors (0/60). All subjects were Japanese. Although 12 of 40 HCC patients were negative for both alpha-fetoprotein (AFP) and PIVKA-II well known tumor markers of HCC, four of these were GPC3-positive in the sera. We also observed vanishing GPC3 protein in the sera of three patients after the surgical treatment for HCC. On the other hand, immunohistochemical analysis revealed that HCC expressed GPC3 protein in all 14 HCC patients tested. In conclusion, GPC3, as defined in this study was shown to be a useful tumor marker for cancer-diagnosis for large numbers of patients with HCC.
Nakatsura
Tetsuya
T
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, 860-8556, Kumamoto, Japan.
Yoshitake
Yoshihiro
Y
Senju
Satoru
S
Monji
Mikio
M
Komori
Hiroyuki
H
Motomura
Yutaka
Y
Hosaka
Seiji
S
Beppu
Toru
T
Ishiko
Takatoshi
T
Kamohara
Hidenobu
H
Ashihara
Hiroshi
H
Katagiri
Toyomasa
T
Furukawa
Yoichi
Y
Fujiyama
Shigetoshi
S
Ogawa
Michio
M
Nakamura
Yusuke
Y
Nishimura
Yasuharu
Y
D000328:Adult; D000368:Aged; D001483:Base Sequence; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000097:blood* / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D012995:Solubility; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000378:metabolism
D015415:Biomarkers; D014408:Biomarkers, Tumor; D017931:DNA Primers; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin