Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma

For detection of hepatocellular carcinoma (HCC) in patients with liver cirrhosis, serum alpha-fetoprotein has been widely used, but its sensitivity has not been satisfactory, especially in small, well-differentiated HCC, and complementary serum marker has been clinically required. Glypican-3 (GPC3),...

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Published in:	Cancer research (Chicago, Ill.) Vol. 64; no. 7; pp. 2418 - 2423
Main Authors:	HIPPO, Yoshitaka, WATANABE, Kiyotaka, NEZU, Jun-Ichi, TSUNODA, Hiroyuki, YOSHINO, Takeshi, OHIZUMI, Iwao, TSUCHIYA, Masayuki, OHNISHI, Shin, MAKUUCHI, Masatoshi, HAMAKUBO, Takao, KODAMA, Tatsuhiko, ABURATANI, Hiroyuki, WATANABE, Akira, MIDORIKAWA, Yutaka, YAMAMOTO, Shogo, IHARA, Sigeo, TOKITA, Susumu, IWANARI, Hiroko, ITO, Yukio, NAKANO, Kiyotaka
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 01-04-2004
Subjects:	Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - immunology Antineoplastic agents Biological and medical sciences Biomarkers, Tumor - blood Biomarkers, Tumor - chemistry Carcinoma, Hepatocellular - blood Enzyme-Linked Immunosorbent Assay Glypicans Humans Immunoblotting Liver Neoplasms - blood Medical sciences Membrane Proteins - blood Membrane Proteins - chemistry Membrane Proteins - immunology Neoplasm Proteins - blood Neoplasm Proteins - chemistry Neoplasm Proteins - immunology Peptide Fragments - chemistry Pharmacology. Drug treatments Sensitivity and Specificity Solubility Tumors Biological marker Digestive diseases Hepatic disease Hepatocellular carcinoma Early stage Malignant tumor Soluble form Fragment Terminal
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Summary:	For detection of hepatocellular carcinoma (HCC) in patients with liver cirrhosis, serum alpha-fetoprotein has been widely used, but its sensitivity has not been satisfactory, especially in small, well-differentiated HCC, and complementary serum marker has been clinically required. Glypican-3 (GPC3), a heparan sulfate proteoglycan anchored to the plasma membrane, is a good candidate marker of HCC because it is an oncofetal protein overexpressed in HCC at both the mRNA and protein levels. In this study, we demonstrated that its NH(2)-terminal portion [soluble GPC3 (sGPC3)] is cleaved between Arg(358) and Ser(359) of GPC3 and that sGPC3 can be specifically detected in the sera of patients with HCC. Serum levels of sGPC3 were 4.84 +/- 8.91 ng/ml in HCC, significantly higher than the levels seen in liver cirrhosis (1.09 +/- 0.74 ng/ml; P < 0.01) and healthy controls (0.65 +/- 0.32 ng/ml; P < 0.001). In well- or moderately-differentiated HCC, sGPC3 was superior to alpha-fetoprotein in sensitivity, and a combination measurement of both markers improved overall sensitivity from 50% to 72%. These results indicate that sGPC3 is a novel serological marker essential for the early detection of HCC.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0008-5472 1538-7445
DOI:	10.1158/0008-5472.can-03-2191