title: Oncofetal antigen glypican-3 as a promising early diagnostic marker for hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is characterized by a multi-cause, multi-stage and multi-focus process of tumor progression. Its prognosis is poor and early diagnosis is of utmost importance. This study was undertaken to investigate the dynamic expression of oncofetal antigen glypican-3 (GPC-3) and GPC-3 mRNA in hepatocarcinogenesis and to explore their early diagnostic value for HCC.
  
  
  METHODS
  A hepatoma model was induced in male Sprague-Dawley rats with 0.05% 2-fluorenylacetamide and confirmed by hematoxylin and eosin staining and gamma-glutamyltransferase (GGT) expression. Total RNA was purified and transcribed into cDNA by reverse transcription. Fragments of the GPC-3 gene were amplified by nested RT-PCR, and confirmed by sequencing. GPC-3 was analyzed by immunohistochemistry, Western blotting or ELISA.
  
  
  RESULTS
  Positive GPC-3 expression showed as brown granule-like staining localized in the cytoplasm. Histological examination of hepatocytes revealed three morphological stages of granule-like degeneration, atypical hyperplasia (precancerous), and cancer formation, with a progressive increase of liver total RNA and GGT expression. The incidence of liver GPC-3 mRNA and GPC-3, and serum GPC-3 was 100%, 100% and 77.8% in the HCC group, 100%, 100%, and 66.7% in the precancerous group, 83.3%, 83.3%, and 38.9% in the degeneration group, and no expression in the liver or blood of the control group, respectively. There was a positive correlation between liver GPC-3 mRNA and total RNA level (r=0.475, P<0.05) or liver GPC-3 (r=1.0, P<0.001) or serum GPC-3 (r=0.994, P<0.001).
  
  
  CONCLUSIONS
  Abnormal oncofetal antigen GPC-3 and GPC-3 mRNA expression in hepatocarcinogenesis may be promising molecular markers for early diagnosis of HCC.
authors.affiliation: Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Deng-Fu
authors.initials: DF
authors.lastname: Yao
authors.forename: Yin-Zhu
authors.initials: YZ
authors.lastname: Bian
authors.forename: Chong-Guo
authors.initials: CG
authors.lastname: Zhang
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Qiu
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Sai
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Yang
authors.forename: Hai-Jian
authors.initials: HJ
authors.lastname: Zhang
mesh_terms: D015073:2-Acetylaminofluorene; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D053673:Glypicans / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006965:Hyperplasia; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D014408:Biomarkers, Tumor; D053673:Glypicans; C105936:Gpc3 protein, rat; D012333:RNA, Messenger; D015073:2-Acetylaminofluorene