title: The beta2-adrenergic receptor is a potential prognostic biomarker for human hepatocellular carcinoma after curative resection.
abstract: BACKGROUND
  The beta2-adrenergic receptor (Beta2-AR) is overexpressed and highly associated with poor prognosis in many malignancies. Nevertheless, the role of Beta2-AR in hepatocellular carcinoma (HCC) has not been thoroughly elucidated. The aim of this study is to investigate the expression of Beta2-AR and its clinicopathological/prognostic value in HCC patients after curative resection.
  
  
  METHODS
  Semiquantitative reverse transcription PCR (RT-PCR) and real-time quantitative PCR (qPCR) were used to measure Beta2-AR RNA expression in 60 pairs of HCC tumors and matched nontumorous tissues. Beta2-AR expression was detected in HCC cell lines by Western blot analysis. Furthermore, we investigated Beta2-AR expression in correlation with the clinicopathological features and analyzed the potential prognostic significance of Beta2-AR in 192 HCC patients by immunohistochemistry (IHC).
  
  
  RESULTS
  Upregulation of Beta2-AR mRNA was significantly higher in HCC tumor tissues than in their paired nontumorous liver specimens. The expression of Beta2-AR protein was detected in five HCC cell lines. Positive Beta2-AR protein expression was significantly associated with a high α-fetoprotein (AFP) level (P = 0.001), large tumor size (P < 0.001), tumor encapsulation (P = 0.002), vascular invasion (P = 0.004), microsatellite formation (P = 0.002), and poor differentiation (P < 0.001). In univariate and multivariate analyses, Beta2-AR was an excellent predictive factor for both recurrence-free survival and overall survival (OS). Beta2-AR expression status was associated with poor prognosis independent of AFP, tumor-node-metastasis stage and Edmondson stage.
  
  
  CONCLUSIONS
  The Beta2-AR is a potential prognostic biomarker for survival and tumor recurrence in HCC patients after curative resection.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
authors.forename: Dongtai
authors.initials: D
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.forename: Jian
authors.initials: J
authors.lastname: Hong
authors.forename: Meibing
authors.initials: M
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Huang
authors.forename: Cuizhen
authors.initials: C
authors.lastname: Zhu
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Yuan
authors.forename: Weian
authors.initials: W
authors.lastname: Zeng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001808:Blood Vessels / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D000509:alpha-Fetoproteins