title: HMGA1 Expression in Human Hepatocellular Carcinoma Correlates with Poor Prognosis and Promotes Tumor Growth and Migration in in vitro Models.
abstract: BACKGROUND
  HMGA1 is a non-histone nuclear protein that regulates cellular proliferation, invasion and apoptosis and is overexpressed in many carcinomas. In this study we sought to explore the expression of HMGA1 in HCCs and cirrhotic tissues, and its effect in in vitro models.
  
  
  METHODS
  We evaluated HMGA1 expression using gene expression microarrays (59 HCCs, of which 37 were matched with their corresponding cirrhotic tissue and 5 normal liver donors) and tissue microarray (192 HCCs, 108 cirrhotic tissues and 79 normal liver samples). HMGA1 expression was correlated with clinicopathologic features and patient outcome. Four liver cancer cell lines with stable induced or knockdown expression of HMGA1 were characterized using in vitro assays, including proliferation, migration and anchorage-independent growth.
  
  
  RESULTS
  HMGA1 expression increased monotonically from normal liver tissues to cirrhotic tissue to HCC (P<.01) and was associated with Edmondson grade (P<.01). Overall, 51% and 42% of HCCs and cirrhotic tissues expressed HMGA1, respectively. Patients with HMGA1-positive HCCs had earlier disease progression and worse overall survival. Forced expression of HMGA1 in liver cancer models resulted in increased cell growth and migration, and vice versa. Soft agar assay showed that forced expression of HMGA1 led to increased foci formation, suggesting an oncogenic role of HMGA1 in hepatocarcinogenesis.
  
  
  CONCLUSIONS
  HMGA1 is frequently expressed in cirrhotic tissues and HCCs and its expression is associated with high Edmondson grade and worse prognosis in HCC. Our results suggest that HMGA1 may act as oncogenic driver of progression, implicating it in tumor growth and migration potential in liver carcinogenesis.
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Mariacarla
authors.initials: M
authors.lastname: Andreozzi
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Quintavalle
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Benz
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Quagliata
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Matter
authors.affiliation: Department of Biomedicine, Hepatology Laboratory, University of Basel, Basel, Switzerland.
authors.forename: Diego
authors.initials: D
authors.lastname: Calabrese
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Nadia
authors.initials: N
authors.lastname: Tosti
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Ruiz
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Trapani
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), and Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II, Naples, Italy; National Cancer Institute-INCA, Rua Andrè Cavalcanti, 37-Centro, Rio de Janeiro, Brazil.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.affiliation: Department of Biomedicine, Hepatology Laboratory, University of Basel, Basel, Switzerland.
authors.forename: Markus H
authors.initials: MH
authors.lastname: Heim
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Charlotte Ky
authors.initials: CK
authors.lastname: Ng
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland; Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), and Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II, Naples, Italy.
authors.forename: Pierlorenzo
authors.initials: P
authors.lastname: Pallante
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland. Electronic address: Luigi.Terracciano@usb.ch.
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Terracciano
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland. Electronic address: Salvatore.Piscuoglio@usb.ch.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Piscuoglio
mesh_terms: D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D024003:HMGA Proteins / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D024003:HMGA Proteins; D012333:RNA, Messenger