title: Yes-associated protein expression is a predictive marker for recurrence of hepatocellular carcinoma after liver transplantation.
abstract: OBJECTIVE
  To explore the expression of Yes-associated protein (YAP) in hepatocellular carcinoma (HCC) patients, and assess its prognostic value to recurrence of HCC after liver transplantation (LT).
  
  
  METHODS
  Collected data of 105 consecutive patients undergoing LT for HCC were analyzed retrospectively. The immunohistochemistry was used to detect the expression of YAP, Mst1, Lats1/2, pYAP, pLats1/2 and pMst1/2 in tumor tissues. Contingency table and χ(2)-test were used to investigate the correlation between expression of YAP, Mst1, Lats1/2 and clinical characteristics. Univariate survival analysis and Multivariate Cox regression analysis were also performed to analyze the correlation of clinical and pathological factors with tumor recurrence after LT. The Kaplan-Meier method and log-rank test were used to analyze HCC-specific disease-free survival (DFS) rate.
  
  
  RESULTS
  Forty patients fulfilled Milan criteria with 1-, 2-, 3- and 5-years DFS of 86.7, 84.6, 84, 84%, respectively. The positive rates of YAP, Lats1/2, Mst1 in HCC were 51.4, 45.7, 64.8%, respectively. YAP expression in HCC tumors was significantly associated with tumor size (p = 0.041), venous infiltration (p = 0.002), AJCC tumor stage (p = 0.027). Lats1/2 expression was significantly associated with tumor size (p = 0.001) and AJCC tumor stage (p = 0.019). Mst1 expression was also significantly associated with tumor size (p = 0.042). HCC-specific DFS was significantly longer for patients with YAP negative expression compared with patients with YAP positive expression (1-, 2-, 3- and 5-years DFS of 71.7, 65.3, 65.3, 65.3 vs. 42.5, 36.6, 32.5, 30.4%, respectively, log-rank = 12.89, p < 0.001). Multivariate Cox regression analysis indicated that YAP expression (HR = 2.011, p = 0.020) in HCC was an independent prognostic factor for HCC-specific DFS after liver transplantation.
  
  
  CONCLUSIONS
  YAP is an independent prognostic marker for tumor recurrence for HCC patients after liver transplantation.
authors: Department of Hepatic Surgery, The Third Afﬁliated Hospital of Sun Yat-sen University, Guangzhou,Guangdong, PR China.
authors: Hua
authors: H
authors: Li
authors: Shouhua
authors: S
authors: Wang
authors: Guoying
authors: G
authors: Wang
authors: ZhiGang
authors: Z
authors: Zhang
authors: Xiaocai
authors: X
authors: Wu
authors: Tong
authors: T
authors: Zhang
authors: Binsheng
authors: B
authors: Fu
authors: Guihua
authors: G
authors: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D017228:Hepatocyte Growth Factor / Q000032:analysis; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry* / Q000473:pathology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000737:chemistry*; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000032:analysis*; D011237:Predictive Value of Tests; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012189:Retrospective Studies; D014157:Transcription Factors; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000032:analysis; D000091102:YAP-Signaling Proteins; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; C092745:LATS1 protein, human; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases