title: Alterations of TP53 are associated with a poor outcome for patients with hepatocellular carcinoma: evidence from a systematic review and meta-analysis.
abstract: BACKGROUND
  The prognostic significance of p53 aberration in hepatocellular carcinoma (HCC) remains inconclusive. This systematic review and meta-analysis aimed to provide comprehensive evidence on the association of p53 alterations with recurrence-free survival (RFS) and overall survival (OS) in HCC patients.
  
  
  METHODS
  Systematic literature searches were conducted until July 2010. Meta-analysis was performed to estimate prognostic effects of p53 alterations on patient outcomes in HCC. Sensitivity and subgroup analyses were also conducted in the meta-analysis.
  
  
  RESULTS
  Thirty-seven studies (7 tumour p53 mutation, 23 tumour p53 expression and 7 serum anti-p53 antibodies) were included in the systematic review and meta-analysis. The average percentages of p53 mutation, p53 expression upregulation and anti-p53 antibody level elevation in HCC patients were 31.5%, 35.0% and 23.8%, respectively. Tumour p53 alterations were associated significantly with poor patient outcomes in HCC: the summary hazard ratio (HR) of mutant p53 versus wild type p53 phenotype was 2.58 [95% confidence interval (CI): 1.96-3.41] for OS and 3.19 [95% CI: 2.21-4.60] for RFS, respectively; and the summary HR of upregulated p53 expression versus low/undetectable p53 expression was 1.68 [95% CI: 1.49-1.90] for OS and 1.89 [95% CI: 1.34-2.66] for RFS, respectively. However, elevated serum anti-p53 antibody was only associated with poor OS in HCC group with a high proportion of (≥ 50%) of hepatitis C virus (HCV) infection [HR: 1.92; 95% CI: 1.30-2.85]. Moreover, sensitivity analyses showed that the results of meta-analyses were not altered.
  
  
  CONCLUSIONS
  HCC patients with p53 mutation and upregulated expression in tumour tissue have a shorter OS and RFS than patients with wild type p53 and low/undetectable p53 expression. However, the prognostic value of serum anti-p53 antibody is required to be further examined.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jiangbo
authors.initials: J
authors.lastname: Liu
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Ma
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Xinshuai
authors.initials: X
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Fengfei
authors.initials: F
authors.lastname: Wang
authors.forename: Erxi
authors.initials: E
authors.lastname: Wu
mesh_terms: D000912:Antibodies, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology
chemical_list: D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53