Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma - PubMed (original) (raw)

. 2004 Apr 1;64(7):2418-23.

doi: 10.1158/0008-5472.can-03-2191.

Kiyotaka Watanabe, Akira Watanabe, Yutaka Midorikawa, Shogo Yamamoto, Sigeo Ihara, Susumu Tokita, Hiroko Iwanari, Yukio Ito, Kiyotaka Nakano, Jun-ichi Nezu, Hiroyuki Tsunoda, Takeshi Yoshino, Iwao Ohizumi, Masayuki Tsuchiya, Shin Ohnishi, Masatoshi Makuuchi, Takao Hamakubo, Tatsuhiko Kodama, Hiroyuki Aburatani

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

Yoshitaka Hippo et al. Cancer Res. 2004.

Abstract

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.

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