title: Recurrence and poor prognosis following resection of small hepatitis B-related hepatocellular carcinoma lesions are associated with aberrant tumor expression profiles of glypican 3 and osteopontin.
abstract: BACKGROUND
  Early detection and following appropriate treatments of hepatocellular carcinoma (HCC) is still the gold standard for favored outcome of HCC patients; nevertheless, a small portion of hepatitis B virus (HBV)-related small HCC (<5 cm) patients got poor prognosis. Furthermore, the study for small HBV-HCC was limited. Therefore, the aim of this study was to explore the potential genetic signature for HBV-related small HCC as novel prognostic factors.
  
  
  METHODS
  We examined expression profiles of HBV-related small HCC using an Affymetrix U133A GeneChip, evaluated differential gene expression by quantitative real-time polymerase chain reaction (qRT-PCR), and finally validated these expression patterns by immunohistochemistry (IHC).
  
  
  RESULTS
  A total of 57 genes were differentially expressed between tumor and normal parts (n = 20 pairs) using Affymetrix U133A chip, and 16 genes were further evaluated by qRT-PCR. The result was compatible with the finding of oligonucleotide microarray (Pearson's correlation, r = 0.87). Furthermore, the expression pattern in HCC tissue by IHC in another group of small HBV-HCC (n = 100) showed overexpression of either osteopontin (OPN) or glypican 3 (GPC3) is an independent prognostic factor for disease-free survival (DFS) in HBV-positive small HCC (P < 0.01 and 0.03, respectively). Long-term DFS and overall survival (OS) for small HBV-HCC patients with high risk (both elevated GPC3(+)/OPN(+)) were DFS 0%, OS 0%, respectively; on the other hand, DFS and OS in patients with moderate (only 1 gene elevated) or low (OPN(-)/GPC3(-)) risk were 35.0 and 46.5%, respectively.
  
  
  CONCLUSIONS
  Elevation of both OPN and GPC3 may act as an adverse indicator for HBV-related small HCC patients after curative resection.
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
authors.forename: Ming-Chin
authors.initials: MC
authors.lastname: Yu
authors.forename: Yun-Shien
authors.initials: YS
authors.lastname: Lee
authors.forename: Sey-En
authors.initials: SE
authors.lastname: Lin
authors.forename: Hsiang-Yao
authors.initials: HY
authors.lastname: Wu
authors.forename: Tse-Ching
authors.initials: TC
authors.lastname: Chen
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Lee
authors.forename: Miin-Fu
authors.initials: MF
authors.lastname: Chen
authors.forename: Chi-Neu
authors.initials: CN
authors.lastname: Tsai
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D002448:Cell Adhesion / Q000235:genetics; D049109:Cell Proliferation; D002633:Chemotaxis / Q000235:genetics; D018572:Disease-Free Survival; D015536:Down-Regulation; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D053673:Glypicans / Q000235:genetics* / Q000378:metabolism; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism; D016016:Proportional Hazards Models; D015854:Up-Regulation
chemical_list: D053673:Glypicans; D053495:Osteopontin