Yes-Associated Protein Expression is a Predictive Marker for Recurrence of Hepatocellular Carcinoma after Liver Transplantation

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 X-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. (C) 2015 S. Karger AG, Basel