title: Gene expression analysis for evaluation of potential biomarkers in hepatocellular carcinoma.
abstract: BACKGROUND
  The poor prognosis of hepatocellular carcinoma (HCC) and the lack of specific screening markers underline the need for new biomarkers for human hepatocarcinogenesis.
  
  
  METHODS
  We investigated 10 postulated biomarkers for HCC (AFP, GPC3, OPN, IGF1, HGF, SPINK1, KPNA, FUCA1, CgA, HSP90) with microarray gene expression analysis and real-time polymerase chain reaction (RT-PCR) in HCC tissues of different etiologies.
  
  
  RESULTS
  Four candidate genes (FUCA1, HGF, IGF1, CgA) showed low median fold changes (fc) of expression compared to corresponding non-malignant liver tissues (fc range=0.2-0.8; maximum 15% of samples). The classic biomarker, alpha-fetoprotein (AFP), was significantly over-expressed (fc=2.4) in 30% of tumors. High tumor AFP expression was associated with significantly elevated serum AFP concentrations (>90% of cases). Five genes (OPN, SPINK1, GPC3, HSP90, KNPA2) showed significantly higher expression than AFP in 64% to 82% of samples (median fc range=2.9-8.3). RT-PCR analyses gave similar results.
  
  
  CONCLUSIONS
  Unlike previous studies, our results did not confirm FUCA1, HGF, IGF1 or CgA as potential markers for HCC. In contrast, OPN, SPINK1, GPC3 and KNPA2 were significantly over-expressed in HCC tissues. These genes may be useful in developing future biomarkers and therapeutic strategies for HCC.
authors: Department of Oncology, Paracelsus Hospital, Scheidegg, Germany dr.holger.hass@paracelsus-kliniken.de
authors: Holger G
authors: HG
authors: Hass
authors: Holger
authors: H
authors: Hass
authors: Department of Oncology, Paracelsus Hospital, Scheidegg, Germany.
authors: Juergen
authors: J
authors: Jobst
authors: Department of Gastroenterology, Hematology, Oncology and Rheumatology, University of Wuerzburg, Wuerzburg, Germany.
authors: Michael
authors: M
authors: Scheurlen
authors: Department of Pathology, University of Tuebingen, Tuebingen, Germany.
authors: Ulrich
authors: U
authors: Vogel
authors: Praxis of Gastroenterology and Tumor Medicine, Stuttgart, Germany.
authors: Oliver
authors: O
authors: Nehls
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D053673:Glypicans / Q000096:biosynthesis*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D053495:Osteopontin / Q000096:biosynthesis*; D011379:Prognosis; D014359:Trypsin Inhibitor, Kazal Pancreatic; D028901:alpha Karyopherins / Q000096:biosynthesis*; D000509:alpha-Fetoproteins / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C105937:GPC3 protein, human; D053673:Glypicans; D009363:Neoplasm Proteins; C486642:SPINK1 protein, human; D028901:alpha Karyopherins; D000509:alpha-Fetoproteins; D053495:Osteopontin; D014359:Trypsin Inhibitor, Kazal Pancreatic
keywords: Hepatocellular carcinoma; alpha-fetoprotein; biomarkers; gene expression analysis; glypican 3; osteopontin