title: Values of circulating GPC-3 mRNA and alpha-fetoprotein in detecting patients with hepatocellular carcinoma.
abstract: BACKGROUND
  The prognosis of hepatocellular carcinoma (HCC) is poor and its early diagnosis is of the utmost importance. This study aimed to investigate the values of glypican-3 (GPC-3) expression in the liver and sera and its gene transcription for diagnosis and monitoring of metastasis of HCC.
  
  
  METHODS
  Liver GPC-3 was analyzed in HCC tissues from 36 patients by immunohistochemistry and Western blotting. GPC-3 mRNA from circulating peripheral blood mononuclear cells from 123 HCC patients or 246 patients with other diseases or 36 HCC tissues was amplified by RT-PCR, quantitative real-time PCR, and confirmed by DNA sequencing. Circulating GPC-3 level was detected by ELISA.
  
  
  RESULTS
  The increasing expression of GPC-3 was observed from non-cancerous to cancerous tissues, with brown granule-like staining localized in tumor parts of atypical hyperplasia and HCC formation. The positive rate of GPC-3 was 80.6% in HCC, 41.7% in their paracancerous tissues, and none in distal cancerous tissues (P<0.001), with no significant difference in differentiation grade and tumor number except for size (Z=2.941, P=0.003). Serum GPC-3 was detected only in HCC (52.8%) and significant difference was found between GPC-3 and tumor size (X2=6.318, P=0.012) or HBV infection (X2=23.362, P<0.001). Circulating GPC-3 mRNA was detected in 70.7% of HCC tissues, with relation to TNM stage, periportal cancerous embolus, and extra-hepatic metastasis (P<0.001). The combination of circulating GPC-3, GPC-3 mRNA and alpha-fetoprotein is of complementary value for HCC diagnosis (94.3%).
  
  
  CONCLUSIONS
  Both GPC-3 overexpression and GPC-3 mRNA abnormality could be used as markers for the diagnosis of HCC and monitoring its metastasis.
authors.affiliation: Department of Immunology, Medical School 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: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Xiao-Di
authors.initials: XD
authors.lastname: Yan
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Yu
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Qiu
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Yang
authors.forename: Hai-Jian
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Sai
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000235:genetics* / Q000556:secondary; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D053673:Glypicans / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000097:blood* / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood*; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: C097353:AFP protein, human; C105937:GPC3 protein, human; D053673:Glypicans; D012333:RNA, Messenger; D000509:alpha-Fetoproteins