title: Prognostic impact of pERK in advanced hepatocellular carcinoma patients treated with sorafenib.
abstract: BACKGROUND
  Sorafenib represents the standard of care targeted therapy for patients with advanced hepatocellular carcinoma (HCC). However, biomolecules that predict a patient's response to sorafenib treatment for HCC remain largely unknown. Thus, this study was designed to investigate whether phosphorylated ERK (pERK) and members of the sorafenib target or PI3K/Akt/mTOR signaling pathway predict the efficacy of sorafenib in advanced HCC patients.
  
  
  METHODS
  From December 2008 to October 2011, pathological specimens from 54 advanced HCC patients received sorafenib treatment were obtained. Clinicopathological variables, treatment response, survival and time to progression (TTP) were recorded. Immunophenotypical analysis was carried out using antibodies against pERK, phosphorylated S6K (pS6K), VEGFR2 and PTEN.
  
  
  RESULTS
  The median overall survival (OS) and TTP were 14.2 and 3.4 months, respectively, and the disease control rate (DCR) was 59.3%. Better Eastern Cooperative Oncology Group Performance Status (ECOG PS) (95% CI: 3.27-4.93 m vs. 1.15-2.85 m, p = 0.01), Child-Pugh class A score (95% CI: 3.47-4.53 vs. 1.14-2.06 m, p < 0.01), and higher pERK (3.34-6.66 m vs. 1.33-2.67 m, p = 0.03) and VEGFR2 (3.49-6.52 m vs. 2.15-2.73 m, p = 0.04) immunohistochemical staining score were associated with increased TTP by univariate analysis. The ECOG PS (p = 0.022), Child-Pugh class (p = 0.045) and pERK staining score (p = 0.012) were found to be associated with TTP using multivariate analysis.
  
  
  CONCLUSIONS
  Sorafenib treatment outcome is favorable in advanced HCC patients who received tumor resection and who have a good ECOG PS and Child-Pugh class A liver function. The pERK immunohistological staining score, ECOG PS and Child-Pugh class may be helpful in determining patients most likely to benefit from sorafenib therapy.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou 510080, Guangdong Province, China.
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: P
authors.initials: P
authors.lastname: Zhao
authors.forename: S Q
authors.initials: SQ
authors.lastname: Li
authors.forename: W K
authors.initials: WK
authors.lastname: Xiao
authors.forename: X Y
authors.initials: XY
authors.lastname: Yin
authors.forename: B G
authors.initials: BG
authors.lastname: Peng
authors.forename: L J
authors.initials: LJ
authors.lastname: Liang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D010766:Phosphorylation; D011379:Prognosis; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D000077157:Sorafenib; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D040301:Vascular Endothelial Growth Factor Receptor-2; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D048049:Extracellular Signal-Regulated MAP Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Hepatocellular carcinoma; Phosphorylated ERK; Prognostic markers; Sorafenib