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

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 χ²-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.

The correlation between poor prognosis and increased yes-associated protein 1 expression in keratin 19 expressing hepatocellular carcinomas and cholangiocarcinomas

“…Nevertheless, we did observe a similar trend in the tumor progression of pT1 stage HCC patients. These results are consistent with previous studies reporting on the prognostic value of activated YAP1 in CCAs and HCCs [28, 29]…”

Downregulation of YAP inhibits proliferation, invasion and increases cisplatin sensitivity in human hepatocellular carcinoma cells

“…YAP has been proven to be upregulated in various types of cancer, including HCC (11,25). In the present study, it was revealed that overexpression of YAP in HCC is associated with the tumor differentiation.…”

The Clinical Significance and Potential Therapeutic Role of GPx3 in Tumor Recurrence after Liver Transplantation

“…Therefore, the plasma GPx3, which is negatively associated with inflammatory environment in the liver graft, was identified to be correlated with prognosis post-transplantation. Recently, a series of novel markers for HCC recurrence after liver transplantation were identified, such as CD147 28, HOTAIR 29, YAP 30 and MALAT1 31. However, they may not possess the therapeutic effect to prevent tumor recurrence.…”