Yes-associated protein expression is a predictive marker for recurrence of hepatocellular carcinoma after liver transplantation

Dig Surg. 2014;31(6):468-78. doi: 10.1159/000370252. Epub 2015 Jan 22.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis*
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Hepatocellular / chemistry*
  • Carcinoma, Hepatocellular / pathology*
  • Disease-Free Survival
  • Female
  • Hepatocyte Growth Factor / analysis
  • Humans
  • Liver Neoplasms / chemistry*
  • Liver Neoplasms / pathology*
  • Liver Transplantation
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / chemistry*
  • Neoplasm Staging
  • Phosphoproteins / analysis*
  • Predictive Value of Tests
  • Protein Serine-Threonine Kinases / analysis
  • Proto-Oncogene Proteins / analysis
  • Retrospective Studies
  • Transcription Factors
  • Tumor Burden
  • Tumor Suppressor Proteins / analysis
  • YAP-Signaling Proteins
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • macrophage stimulating protein
  • Hepatocyte Growth Factor
  • LATS1 protein, human
  • LATS2 protein, human
  • Protein Serine-Threonine Kinases