title: High Serum Transforming Growth Factor-β1 Levels Predict Outcome in Hepatocellular Carcinoma Patients Treated with Sorafenib.
abstract: BACKGROUND
  The TGF-β signaling pathway is crucial in the progression and metastasis of malignancies. We investigated whether the serum TGF-β1 level was related to the outcomes of patients treated with sorafenib for advanced hepatocellular carcinoma (HCC).
  
  
  METHODS
  We selected patients who had received sorafenib-containing regimens as first-line therapy for advanced HCC between 2007 and 2012. Serum TGF-β1 levels were measured and correlated with the treatment outcomes. The expression TGF-β1 and the sensitivity to sorafenib were examined in HCC cell lines.
  
  
  RESULTS
  Ninety-one patients were included; 62 (68%) were hepatitis B virus surface antigen (+), and 11 (12%) were anti-hepatitis C virus (+). High (≥ median) pretreatment serum TGF-β1 levels (median 13.7 ng/mL; range, 3.0-41.8) were associated with high α-fetoprotein levels, but not with age, gender, or disease stage. Patients with high pretreatment serum TGF-β1 levels exhibited significantly shorter progression-free survival (median, 2.5 vs. 4.3 months; P = 0.022) and overall survival (median 5.6 vs. 11.6 months; P = 0.029) than did patients with low serum TGF-β1 levels. Compared with pretreatment levels, the serum TGF-β1 levels were significantly increased at disease progression (n = 29, P = 0.010). In preclinical models of HCC, higher TGF-β1 expression levels were associated with poorer sensitivity to sorafenib.
  
  
  CONCLUSIONS
  High pretreatment serum TGF-β1 levels were associated with poor prognoses, and increased serum TGF-β1 levels were associated with the disease progression of advanced HCC patients. TGF-β pathway may be explored as a therapeutic target for advanced HCC.
authors.affiliation: Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Tzu-Hsuan
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yu-Yun
authors.initials: YY
authors.lastname: Shao
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Soa-Yu
authors.initials: SY
authors.lastname: Chan
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. chihhunghsu@ntu.edu.tw.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D012333:RNA, Messenger / Q000096:biosynthesis; D000077157:Sorafenib; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D009536:Niacinamide; D000077157:Sorafenib