title: Methylation of tissue factor pathway inhibitor 2 as a prognostic biomarker for hepatocellular carcinoma after hepatectomy.
abstract: OBJECTIVE
  Methylation of tissue factor pathway inhibitor 2 (TFPI2) gene has been detected in hepatocellular carcinoma (HCC). However, the clinicopathologcial significance and prognostic value of TFPI2 methylation in HCC remains largely unknown. This study aimed to investigate the prognostic value of TFPI2 methylation in HCC after hepatectomy.
  
  
  METHODS
  Methylation status of TFPI2 gene was examined in 178 surgical specimens of HCC and 20 normal liver samples using methylation-specific polymerase chain reaction.
  
  
  RESULTS
  Methylation of TFPI2 gene was detected in 44.9% (80 of 178) of primary HCC samples, 10.7% (19 of 178) of the corresponding non-tumorous liver samples, and 5.0% (1/20) of the normal liver samples. The mRNA concentrations of TFPI2 in primary HCC tissues were significantly lower than those in corresponding non-tumorous liver tissues and those in normal liver tissues. TFPI2 methylation was significantly associated with higher TNM stage. Patients with TFPI2 methylation demonstrated a significantly poorer prognosis than those without TFPI2 methylation for both overall survival and disease-free survival (P < 0.001, respectively). Multivariate analyses confirmed that TFPI2 methylation was an independent prognostic factor for both overall survival (P = 0.002) and disease-free survival (P = 0.000) in HCC after hepatectomy. Moreover, TFPI2 methylation was found to be the only independent predictor for early tumor recurrence of HCC after resection based on multivariate analysis (P = 0.002).
  
  
  CONCLUSIONS
  Methylation of TFPI2 predicts high risk of advanced tumor stage, early tumor recurrence, and poor prognosis, and it could be a potential prognostic biomarker in patients with HCC after hepatectomy.
authors: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors: Feng-Kai
authors: FK
authors: Sun
authors: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan, China.
authors: Qi
authors: Q
authors: Sun
authors: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.|Institute of Hepatology, Shandong University, Jinan, China.
authors: Yu-Chen
authors: YC
authors: Fan
authors: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors: Shuai
authors: S
authors: Gao
authors: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors: Jing
authors: J
authors: Zhao
authors: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors: Feng
authors: F
authors: Li
authors: Department of Oncology, Qilu Hospital of Shandong University, Jinan, China.
authors: Yi-Bin
authors: YB
authors: Jia
authors: Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China.
authors: Chuan
authors: C
authors: Liu
authors: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors: Li-Yuan
authors: LY
authors: Wang
authors: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors: Xin-You
authors: XY
authors: Li
authors: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors: Xiang-Fen
authors: XF
authors: Ji
authors: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.|Institute of Hepatology, Shandong University, Jinan, China.
authors: Kai
authors: K
authors: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006498:Hepatectomy / Q000401:mortality; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery*; D008297:Male; D008745:Methylation; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D011379:Prognosis; D012306:Risk; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D006023:Glycoproteins; C021240:tissue-factor-pathway inhibitor 2
keywords: early tumor recurrence; hepatocellular carcinoma; methylation; prognosis; tissue factor pathway inhibitor 2