Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker☆
Section snippets
Materials and methods
cDNA microarrays. Profiling of gene expression by cDNA microarrays was done, as reported [4]. Primary HCCs and corresponding non-cancerous liver tissues were obtained with informed consent from 20 Japanese patients who underwent hepatectomy in the Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine. These specimens were used only for cDNA microarray analysis, as reported [4]. Poly(A)+ RNAs isolated from human bone marrow, brain, heart, kidney, liver, lung,
Identification of the GPC3 gene over-expressed specifically in HCC
We obtained data comparing expression profiles between 20 HCCs (10 cases were hepatitis B virus (HBV)-positive and 10 were hepatitis C virus (HCV)-positive) and their corresponding non-cancerous liver tissues [4] and in various normal human tissues [6], using cDNA microarrays. We then searched for genes over-expressed specifically in HCC using these data and we identified GPC3. In 16 cases of the 20 HCCs, the expression of GPC3 mRNA in the cancer tissue was 5 or more times higher than that in
Discussion
In 1996, Pilia et al. reported that GPC3, which encodes one member of the glypican family, is mutated in patients with Simpson–Golabi–Behmel syndrome (SGBS) [9]. SGBS is an X-linked disorder characterized by pre- and postnatal overgrowth, and a broad spectrum of clinical manifestations which vary from a very mild phenotype in carrier females to infantile lethal forms in some males [10]. The list of clinical manifestations of SGBS includes a distinct facial appearance, cleft palate, syndactyly,
Acknowledgements
This work was supported in part by Grants-in-Aid 60715 and 12213111 from the Ministry of Education, Science, Technology, Sports and Culture, Japan, and by a grant from the Sagawa Science and Technology Promotion Foundation, Japan. We thank T. Kubo (Department of Molecular Pathology, Kumamoto University) for technical assistance of immunohistochemical analyses and M. Ohara (Fukuoka) for helpful comments.
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Abbreviations: HCC, hepatocellular carcinoma; GPC3, glypican-3; HD, healthy donor; LC, liver cirrhosis; CH, chronic hepatitis; AIH, autoimmune hepatitis; PBC, primary biliary cirrhosis; AFP, α-fetoprotein; PIVKA-II, protein induced by vitamin K absence or antagonist-II.