Effects of Hippo pathway component on tumor recurrence after liver transplantation
10.3760/cma.j.issn.1673-9752.2014.05.006
- VernacularTitle:Hippo信号通路相关蛋白对肝癌肝移植术后肿瘤复发的影响
- Author:
Shouhua WANG
;
Hua LI
;
Zhigang ZHANG
;
Xiaocai WU
;
Guoying WANG
;
Guihua CHEN
- Publication Type:Journal Article
- Keywords:
Liver neoplasms;
Liver transplantation;
YAP protein;
Tumor recurrence
- From:Chinese Journal of Digestive Surgery
2014;13(5):345-351
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expression of Hippo pathway component in hepatic cancer tissues and investigate its effects on the tumor recurrence after Iiver transplantation.Methods The clinical data of 105 patients with liver cancer who were admitted to the Third Affiliated Hospital of Sun Yat-Sen University from July 2004 to September 2009 were retrospectively analyzed.The samples of liver cancer tissues were collected.The maximum diameter,number of foci,blood vessel involvement,preoperative level of alpha-fetoprotein (AFP),results of postoperative pathological examination were analyzed.All the patients were followed up via out-patient examination,mail and phone call.Patients were followed up once a week within the first month after operation,and once a month within the 6 months after operation,and then once every 3 months at 1 year later.The follow-up ended in December 2012 or tumor recurrence.The disease-free survival time began at the date of operation and ended at the time of tumor recurrence.The expressions of Yes-associated protein (YAP),phosphorylated YAP,Hippo pathway component (Lats1/2,pLats1/2,Mst1,pMst1/2) were detected by immunohistochemical staining.All data were analyzed using the chi-square test or Student t test.Factors might influence the postoperative tumorfree survival time after liver transplantation were analyzed using the Cox regression model.The survival curve was drawn by Kaplan-Meier method,and the disease-free survival was analyzed using Log-rank test.Results Positive expressions of YAP and phosphorylated YAP were detected in the nucleus and cytoplasm,and the positive expressions of Lats1/2,pLats1/2,Mst1 and pMst1/2 were detected in the cytoplasm.The positive expressions of YAP,phosphorylated YAP,Latsl/2,pLats1/2,Mst1 and pMst1/2 protein were 51.43％ (54/105),55.24％ (58/105),45.71％ (48/105),9.52％ (10/105),64.76％ (68/105) and 20.00％ (21/105),respectively.The positive expression of YAP was correlated with the tumor diameter,venous infiltration and AJCC stage (x2=4.173,9.611,7.233,P ＜ 0.05).The positive expression of Lats1/2 protein was correlated with tumor diameter and AJCC stages (x2=14.413,7.969,P ＜ 0.05).The positive expression of Mst1 protein was correlated with the tumor diameter (x2=4,129,P ＜0.05).The results of univariate analysis showed that the protein expressions of YAP,Lats1/2,pMst1/2,age,tumor diameter,tissue differentiation,preoperative level of AFP,venous infiltration and AJCC stages were risk factors influencing tumor recurrence after liver transplantation (HR =2.603,0.502,1.802,0.955,3.559,2.395,2.414,2.915,2.086,95％ CI:1.452-4.666,0.287-0.880,1.040-3.123,0.931-0.981,1.921-6.595,1.475-3.889,1.313-4.337,1.604-5.229,1.370-3.176,P ＜ 0.05).The results of multivariate analysis showed that the positive expression of YAP,tumor diameter ＞ 5 cm,low differentiation of tissue and AJCC stages Ⅲ were independent risk factors influencing tumor recurrence after liver transplantation (HR=2.011,2.176,2.390,1.574,95％CI:1.115-3.628,1.125-4.206,1.448-3.945,1.041-2.381,P ＜ 0.05).The median time of follow-up was 13.0 months (range,1.0-96.0 months).Eight patients missed follow-up.Fifty-four patients had tumor recurrence,and the mean time of tumor recurrence was 6.7 months (range,1.0-41.0 months).The disease-free survival time of patients with positive expression of YAP were significantly shorter than those with negative expression of YAP (Log-rank value =12.890,P ＜ 0.05).Conclusions Positive expressions of YAP and phosphorylated YAP were detected in the nucleus and cytoplasm,and the positive expressions of Lats1/2,pLats1/2,Mst1 and pMst1/2 were detected in the cytoplasm.The positive expression of YAP is the independent risk factor for tumor recurrence after liver transplantation.
