title: Identification of histone deacetylase 3 as a biomarker for tumor recurrence following liver transplantation in HBV-associated hepatocellular carcinoma.
abstract: BACKGROUND
  Recent studies have shown that high expression levels of class I histone deacetylases (HDACs) correlate with malignant phenotype and poor prognosis in some human tumors. However, the expression patterns and prognostic role of class I HDAC isoforms in hepatocellular carcinoma (HCC) remain unclear.
  
  
  RESULTS
  The expression patterns and clinical significance of class I HDAC isoforms were assessed by immunohistochemistry in a cohort of 43 hepatitis B virus-associated HCC patients treated with liver transplantation. In addition, the effects of HDAC inhibition on HCC cell behavior were investigated by knockdown of the HDAC isoform with short interfering RNA. Class I HDACs were highly expressed in a subset of HCCs with positivity for HDAC1 in 51.2%, HDAC2 in 48.8%, and HDAC3 in 32.6% of cases. The expression levels of HDAC isoforms were significantly associated with the proliferation index of HCC. Kaplan-Meier curves showed that a high expression level of HDAC2 or HDAC3 implicated significantly reduced recurrence-free survival. Cox proportional hazards model analysis revealed HDAC3 overexpression was an unfavorable independent prognostic factor (P = 0.002; HR 3.907). In vitro, inhibition of HDAC2 and HDAC3, but not HDAC1, suppressed proliferation and the invasiveness of liver cancer cells.
  
  
  CONCLUSIONS
  Our findings demonstrate that HDAC3 plays a significant role in regulating tumor cell proliferation and invasion, and it could be served as a candidate biomarker for predicting the recurrence of hepatitis B virus-associated HCC following liver transplantation and a potential therapeutic target.
authors.affiliation: Key Lab of Combined Multi-Organ Transplantation, Key Lab of Organ Transplantation, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Wu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Xie
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Feng
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Shu-Sen
authors.initials: SS
authors.lastname: Zheng
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D049109:Cell Proliferation; D006509:Hepatitis B / Q000150:complications; D006515:Hepatitis B virus; D056284:Histone Deacetylase 1 / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000378:metabolism; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D016031:Liver Transplantation; D009361:Neoplasm Invasiveness; D020033:Protein Isoforms; D034741:RNA, Small Interfering / Q000378:metabolism; D012008:Recurrence; D000099186:Histone Deacetylase 3
chemical_list: D014408:Biomarkers, Tumor; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D000099186:Histone Deacetylase 3; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human