title: Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma.
abstract: BACKGROUND
  We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort.
  
  
  METHODS
  In the current retrospective cohort study, we measured serum levels of the eight cytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21-2.81), and OS (HR, 1.95; 95% CI, 1.21-3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30-3.06) and OS (HR, 1.94; 95% CI, 1.19-3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis.
  
  
  CONCLUSIONS
  High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama-city, Okayama 700-8558, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miyahara
authors.forename: K
authors.initials: K
authors.lastname: Nouso
authors.forename: Y
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: H
authors.initials: H
authors.lastname: Hagihara
authors.forename: K
authors.initials: K
authors.lastname: Kuwaki
authors.forename: H
authors.initials: H
authors.lastname: Onishi
authors.forename: F
authors.initials: F
authors.lastname: Ikeda
authors.forename: Y
authors.initials: Y
authors.lastname: Miyake
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Shiraha
authors.forename: A
authors.initials: A
authors.lastname: Takaki
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Obi
authors.forename: S
authors.initials: S
authors.lastname: Iwadou
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Takaguchi
authors.forename: K
authors.initials: K
authors.lastname: Kariyama
authors.forename: Y
authors.initials: Y
authors.lastname: Takuma
authors.forename: H
authors.initials: H
authors.lastname: Takabatake
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042702:Angiopoietin-2 / Q000097:blood; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000098:blood supply / Q000188:drug therapy; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000098:blood supply / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D012189:Retrospective Studies; D000077157:Sorafenib
chemical_list: D042702:Angiopoietin-2; D000970:Antineoplastic Agents; D016207:Cytokines; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
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