title: PEBP1 downregulation is associated to poor prognosis in HCC related to hepatitis B infection.
abstract: OBJECTIVE
  Phosphatidylethanolamine-binding protein 1 (PEBP1, also RKIP) plays a pivotal role in cancer by regulating multiple cellular signaling processes and suppressing metastasis in animal models. We examined whether PEBP1 expression in hepatocellular carcinoma (HCC) correlated with the risk of recurrence and survival after resection.
  
  
  METHODS
  A randomly selected cohort of 240 Chinese HCC patients, predominantly hepatitis B related, formed the basis of the study. PEBP1 expression levels were evaluated by immunohistochemistry and real-time reverse-transcriptase PCR. Survival analysis was performed by univariate and multivariate analyses. The results were further validated in an independent series of 403 patients. The relevance of PEBP1 to phospho-ERK was determined by Western blot analysis on clinical samples and hepatoma cell lines.
  
  
  RESULTS
  PEBP1, prevalently down-regulated in HCC, was significantly associated with tumor invasive characteristics (such as vascular invasion, lack of encapsulation, poor differentiation and large size). Both PEBP1 protein and mRNA levels were independent predictors for tumor recurrence (hazard ratio (HR) = 1.877, p=0.001; HR = 2.633, p = 0.001; respectively), and patient survival (HR = 1.796, p = 0.004; HR = 1.730, p = 0.044; respectively). The prognostic value of PEBP1 was then confirmed in the validation cohort. In addition, Western blot suggested that loss of PEBP1 led to hyperactivity of MAPK signaling.
  
  
  CONCLUSIONS
  Down-regulation of PEBP1 in HCC indicated aggressive tumor behaviors and predicted a worse clinical outcome, which may be a useful biomarker to identify the patients at high risk of post-operative recurrence.
authors.affiliation: Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yong-Feng
authors.initials: YF
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Yi
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Li
authors.forename: Chen-Xin
authors.initials: CX
authors.lastname: Dai
authors.forename: Ming-Yan
authors.initials: MY
authors.lastname: Cai
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Ju
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Bo-Heng
authors.initials: BH
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000401:mortality; D045744:Cell Line, Tumor; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000401:mortality; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology; D049488:Phosphatidylethanolamine Binding Protein / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D011379:Prognosis
chemical_list: C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases