Clinicopathological and prognostic significance of Yes-associated protein expression in hepatocellular carcinoma and hepatic cholangiocarcinoma

被引:38
作者
Wu, Hao [1 ]
Liu, Yan [2 ]
Jiang, Xiao-Wei [3 ]
Li, Wen-Fang [4 ]
Guo, Gang [5 ]
Gong, Jian-Ping [1 ]
Ding, Xiong [1 ]
机构
[1] Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 2, Chongqing 400010, Peoples R China
[2] Fifth Peoples Hosp Chengdu, Dept Gastroenterol, Chengdu 611130, Peoples R China
[3] Fifth Peoples Hosp Chongqing, Dept Gen Surg, Chongqing 400062, Peoples R China
[4] Hubei Med Univ, Dept Gen Surg, Taihe Hosp, Shiyan 442000, Peoples R China
[5] Sichuan Univ, Pathol Lab, West China Hosp, Chengdu 610041, Peoples R China
基金
中国国家自然科学基金;
关键词
Hepatocellular carcinoma; Hepatic cholangiocarcinoma; Yes-associated protein(YAP); Immunohistochemistry; HIPPO PATHWAY; GROWTH-CONTROL; SIZE-CONTROL; YAP; CANCER; MARKER; TAZ; OVEREXPRESSION; PROLIFERATION; PROGRESSION;
D O I
10.1007/s13277-016-5211-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Hepatocellular carcinoma (HCC) and hepatic cholangiocarcinoma (CC) are the most aggressive malignancies with a poor prognosis in humans, and hepatic cholangiocarcinoma (CC) exhibits greater malignant behaviour. Yes-associated protein (YAP) is an important downstream target of the Hippo signalling pathway. As an oncogene, it plays a vital role in the occurrence and development of tumours. Our study focuses on the clinical significance of YAP protein expression in HCC and CC. Furthermore, we sought to explore the different survival rates between HCC and CC. A total of 137 patients with HCC and 122 with CC after resection were evaluated by immunohistochemistry for the expression of YAP. Our results showed that positive expression rates of YAP were more frequently noted in CC 67.2 % (82/122) than in HCC 56.9 % (78/137) (P = 0.024). High YAP expression in HCC and CC was significantly associated with tumour size (P < 0.001 and P = 0.019, respectively), liver cirrhosis (P = 0.002 and P = 0.009, respectively), vascular invasion (P = 0.047 and P = 0.018, respectively), multiplicity (P = 0.019 and P = 0.015, respectively), and intrahepatic metastasis (P = 0.015 and P = 0.047, respectively). Importantly, recurrence-free survival and disease-specific survival rates were lower in CC with high YAP expression than in HCC with high YAP expression (P < 0.001 and P < 0.001, respectively). Overall, high YAP expression was more frequently found in CC than in HCC, and YAP overexpression was associated with poor survival rates in patients with HCC and CC. Targeting YAP treatment requires further prospective investigations in larger patient populations.
引用
收藏
页码:13499 / 13508
页数:10
相关论文
共 30 条
[1]  
[Anonymous], 2015, Cancer
[2]   YAP oncogene overexpression supercharges colon cancer proliferation [J].
Avruch, Joseph ;
Zhou, Dawang ;
Bardeesy, Nabeel .
CELL CYCLE, 2012, 11 (06) :1090-1096
[3]   Hepatocellular carcinoma epidemiology [J].
Bosetti, Cristina ;
Turati, Federica ;
La Vecchia, Carlo .
BEST PRACTICE & RESEARCH CLINICAL GASTROENTEROLOGY, 2014, 28 (05) :753-770
[4]   Structural and functional insights into the TEAD-YAP complex in the Hippo signaling pathway [J].
Chen, Liming ;
Loh, Portia Gloria ;
Song, Haiwei .
PROTEIN & CELL, 2010, 1 (12) :1073-1083
[5]   Elucidation of a universal size-control mechanism in Drosophila and mammals [J].
Dong, Jixin ;
Feldmann, Georg ;
Huang, Jianbin ;
Wu, Shian ;
Zhang, Nailing ;
Comerford, Sarah A. ;
Gayyed, Mariana F. ;
Anders, Robert A. ;
Maitra, Anirban ;
Pan, Duojia .
CELL, 2007, 130 (06) :1120-1133
[6]   From cell structure to transcription: Hippo forges a new path [J].
Edgar, BA .
CELL, 2006, 124 (02) :267-273
[7]   A Combination of α-Fetoprotein and Des-γ-Carboxy Prothrombin Is Superior in Detection of Hepatocellular Carcinoma [J].
Ertle, Judith M. ;
Heider, Dominik ;
Wichert, Marc ;
Keller, Benedikt ;
Kueper, Robert ;
Hilgard, Philip ;
Gerken, Guido ;
Schlaak, Joerg F. .
DIGESTION, 2013, 87 (02) :121-131
[8]   Tumor suppressor LATS1 is a negative regulator of oncogene YAP [J].
Hao, Yawei ;
Chun, Alex ;
Cheung, Kevin ;
Rashidi, Babak ;
Yang, Xiaolong .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (09) :5496-5509
[9]   The Hippo pathway and human cancer [J].
Harvey, Kieran F. ;
Zhang, Xiaomeng ;
Thomas, David M. .
NATURE REVIEWS CANCER, 2013, 13 (04) :246-257
[10]   The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression [J].
He, Chunbo ;
Mao, Dagan ;
Hua, Guohua ;
Lv, Xiangmin ;
Chen, Xingcheng ;
Angeletti, Peter C. ;
Dong, Jixin ;
Remmenga, Steven W. ;
Rodabaugh, Kerry J. ;
Zhou, Jin ;
Lambert, Paul F. ;
Yang, Peixin ;
Davis, John S. ;
Wang, Cheng .
EMBO MOLECULAR MEDICINE, 2015, 7 (11) :1426-1449