title: Increased adiponectin associated with poor survival in hepatocellular carcinoma.
abstract: BACKGROUND
  Alterations of adiponectin (APN), one of the adipokines, have been associated with human cancers. However, the clinical significance and impacts of APN on hepatocellular carcinoma (HCC) remain undetermined.
  
  
  METHODS
  Using immunohistochemistry, expression patterns of APN were semiquantitatively scored and further statistically correlated with clinicopathological characteristics and patient survival. Furthermore, the bioeffects and underlying mechanisms of ectopic APN overexpression were determined in Hep3B and HepG2 cells by XTT, immunoblotting, flowcytometry, and invasion assays with or without chemical inhibitors and neutralization antibody.
  
  
  RESULTS
  We found that cytoplasmic APN staining in 85 cancerous lesions was increased and associated with a poor survival rate (P = 0.007), even when using the Cox regression model (OR = 3.590; 95 % CI = 1.240-10.394; P = 0.018). Ectopic overexpression of APN in Hep3B and HepG2 cells increased proliferation and invasion as well as the levels of p-AKT (Ser473), p-STAT3 (Tyr705), and those downstream, i.e., cyclin D1 and β-catenin. Similar results were also demonstrated in a stable APN-overexpressing clone, HepG2#136. APN neutralization antibody and LY294002 blocked the APN-mediated effects via inhibition of activated AKT.
  
  
  CONCLUSIONS
  Our results suggest that increased APN may contribute to HCC at least in part through its activation of AKT signalling and may serve as a prognostic factor in HCC.
authors.affiliation: Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Ziyou 1st Rd., Sanmin Dist., Kaohsiung, 80756, Taiwan, ROC.
authors.forename: Shen-Nien
authors.initials: SN
authors.lastname: Wang
authors.forename: Sheau-Fang
authors.initials: SF
authors.lastname: Yang
authors.forename: Hsin-Hui
authors.initials: HH
authors.lastname: Tsai
authors.forename: King-Teh
authors.initials: KT
authors.lastname: Lee
authors.forename: Yao-Tsung
authors.initials: YT
authors.lastname: Yeh
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D052242:Adiponectin; D051057:Proto-Oncogene Proteins c-akt