Yes相关蛋白在肝细胞癌与胆管细胞癌中的表达特征及其与预后的关系

王春; 邬昊; 刘彦; 丁雄; 李泽民

doi:10.3969/j.issn.1001-5256.2017.07.021

Yes相关蛋白在肝细胞癌与胆管细胞癌中的表达特征及其与预后的关系

DOI: 10.3969/j.issn.1001-5256.2017.07.021

1. 重庆永川区中医院外科
2. 重庆医科大学附属第二医院肝胆外科
3. 重庆市彭水县人民医院外科

基金项目:

重庆市卫计委重点项目资助(2015ZDXM012);重庆市卫计委科研资助项目(2016MSXM206)；

详细信息

中图分类号: R735
计量
- 文章访问数: 2373
- HTML全文浏览量: 41
- PDF下载量: 459
- 被引次数: 0
出版历程
- 收稿日期: 2017-01-06
- 出版日期: 2017-07-20

Expression features and prognostic significance of Yes-associated protein in hepatocellular carcinoma and cholangiocellular carcinoma

Department of Surgery, Yongchuan Hospital of Traditional Chinese Medicine

Research funding:

摘要

摘要: 目的探讨Yes相关蛋白（YAP蛋白）在肝细胞癌与胆管细胞癌中的表达与患者临床预后的相关性。方法收集2004年7月-2009年7月重庆医科大学附属第二医院收治的190例肝癌患者标本,其中肝细胞癌110例,胆管细胞癌80例。分析不同组别YAP蛋白表达水平的差异,比较不同组别患者的预后情况。YAP蛋白的表达与肝细胞癌、胆管细胞癌患者临床病理特征之间关系比较采用χ2检验。采用Kaplan-Meier与log-rank检验分析患者的无瘤生存率与总生存率。采用Cox回归分析YAP蛋白的表达对肝细胞癌与胆管细胞癌患者预后的影响。结果 YAP蛋白在胆管细胞癌中的高表达率为68.7%,比肝细胞癌中的高表达率（56.3%）高。在肝细胞癌与胆管细胞癌中,YAP蛋白的高表达在不同肿瘤大小（P值分别为<0.001、0.024）、不同AFP水平（P值分别为0.009、0.034）、是否有肝硬化（P值分别为0.032、0.006）、是否存在血管侵犯（P值分别为0.011、0.028）和肝内转移（P值分别为0.049、0.030）的患者间,差异均有统计学意义。在肝细胞癌与胆管细胞癌患者中,...
- 肝肿瘤,实验性 /
- Yes相关蛋白 /
- 预后
Abstract: Objective To investigate the expression of Yes-associated protein (YAP) in hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CC) and its association with clinical prognosis.Methods Samples were collected from 190 patients who were treated in The Second Hospital Affiliated to Chongqing Medical University from July 2004 to July 2009, among whom 110 had HCC and 80 had CC.The difference in YAP expression and its association were analyzed in both groups, and patients' prognosis was compared between the two groups.The chi-square test was used to investigate the association between YAP expression and clinicopathological features of HCC and CC, and the Kaplan-Meier method and the log-rank test were used to assess tumor-free survival rate and overall survival rate.A univariate Cox regression analysis was used to evaluate the influence of YAP expression on the prognosis of patients with HCC and CC.Results The CC group had higher expression of YAP than the HCC group (68.7% vs 56.3%, P=0.036) .High YAP expression in HCC and CC was significantly associated with tumor size (P<0.001 and P=0.024) , alpha fetoprotein (P=0.009 and 0.034) , liver cirrhosis (P=0.032 and 0.006) , vascular invasion (P=0.011 and 0.028) , and intrahepatic metastasis (P=0.049 and 0.030) .In both groups, the patients with high YAP expression had significantly lower tumor-free survival rate and overall survival rate than those with low YAP expression (all P<0.05) .Multivariate analysis showed that high YAP expression is an adverse prognostic factor for tumor-free survival and overall survival in both groups (all P<0.05) .Conclusion High YAP expression is frequently found in patients with HCC and CC, and high YAP expression is associated with low survival rate.
- liver neoplasms, experimenal /
- Yes-associated protein /
- prognosis

HTML全文

参考文献(28)

[1]MEDIA CENTRE.Title of subordinate document.In:Cancer, 2015[EB/OL]. (2015-02-18) http//www.who.int/mediacentre/factsheets/fs297/en/.

[2]KOH KC, LEE H, CHOI MS, et al.Clinicopathologic features and prognosis of combined hepatocellular cholangiocarcinoma[J].Am JSurg, 2005, 189 (1) :120-125.

[3]WANG J, WANG F, KESSINGER A.Outcome of combined hepatocellular and cholangiocarcinoma of the liver[J].J Oncol, 2010, 2010:917356.

[4]ERTLE JM, HEIDER D, WICHERT M, et al.A combination of alpha-fetoprotein and des-gamma-carboxy prothrombin is superior in detection of hepatocellular carcinoma[J].Digestion, 2013, 87 (2) :121-131.

[5]YANG H, ZHAI G, JI X, et al.LAPTM4B allele*2 is a marker of poor prognosis following hepatic tumor resection for hepatocellular carcinoma[J].PLo S One, 2012, 7 (4) :e34984.

[6]JOHNSON R, HALDER G.The two faces of Hippo:targeting the Hippo pathway for regenerative medicine and cancer treatment[J].Nat Rev Drug Discov, 2014, 13 (1) :63-79.

[7]HARVEY KF, ZHANG X, THOMAS DM.The Hippo pathway and human cancer[J].Nat Rev Cancer, 2013, 13:246-257.

[8]MENG Z, MOROISHI T, GUAN KL.et al.Mechanisms of Hippo pathway regulation[J].Genes Dev, 2016, 30 (1) :1-17.

[9]DING R, KEVIN W, TORSTEN B.The Hippo signalling pathway maintains quiescence in Drosophila neural stem cells[J].Nat Commun, 2016, 7:10510.

[10]KIM JE, FINLAY GJ, BAGULEY BC.The role of the hippo pathway in melanocytes and melanoma[J].Front Oncol, 2013, 3:123.

[11]KOMURO A, NAGAI M, NAVIN NE et al.WW domain-containing protein YAP ssociateswith Erb B-4 and acts as a co-transcriptional activator for the carboxyl-terminal ragment of Erb B-4that translocates to the nucleus[J].J Biol Chem, 2003, 278:33334-33341.

[12]NALLET-STAUB F, MARSAUD V, LI L, et al.Pro-invasive activity of the Hippo pathway effectors YAP and TAZ in cutaneous melanoma[J].J Invest Dermatol, 2014, 134 (1) :123.

[13]MORVARIDI S, DHALL D, GREENE M, et al.Role of YAP and TAZ in pancreatic ductal adenocarcinoma and in stellate cells associated with cancer and chronic pancreatitis[J].Sci Rep, 2015, 16 (5) :16759.

[14]ZENDER L, SPECTOR MS, XUE W, et al.Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach[J].Cell, 2006, 125:1253-1267.

[15]CHUNBO HE, DAGAN MAO, GUOHUA HUA, et al.The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression[J].EMBO Mol Med, 2015, 7 (11) :1426-1449.

[16]MAUGERI-SACCM, BARBA M, PIZZUTI L, et al.The Hippo transducers TAZ and YAP in reast cancer:oncogenic activities and clinical implications[J].Expert Rev Mol Med, 2015, 17:e14.

[17]WANG Y, DONG Q, ZHANG Q, et al.Overexpression of yesassociated protein contributes to progression and poor prognosis of nonsmall-cell lung cancer[J].Cancer Sci, 2010, 101 (5) :1279-1285.

[18]KANG W, TONG JH, CHAN AW.Yes-associated protein 1 exhibits oncogenic property in gastric cancer and its nuclear accumulation associates with poor prognosis[J].Clin Cancer Res, 2011, 17 (8) :2130-2139.

[19]AVRUCH J, ZHOU D, BARDEESY N.YAP oncogene overexpression supercharges colon cancer proliferation[J].Cell Cycle, 2012, 11 (6) :1090-1096.

[20]KIM M, KIM T, JOHNSON RL, et al.Transcriptional co-repressor function of the hippo pathway transducers YAP and TAZ[J].Cell Rep, 2015, 11 (2) :270-282.

[21]WANG Y, XIE C, LI Q, et al.Clinical and prognostic significance of Yes-associated protein in colorectal cancer[J].Tumor Biol, 2013, 34 (4) :2169-2174.

[22]ZHAO B, WEI X, LI W, et al.Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control[J].Genes Dev, 2007, 21:2747-2761.

[23] XU MZ, YAO TJ, LEE NP, et al.Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma[J].Cancer, 2009, 115 (9) :4576-4585.

[24]DONG J, FELDMANN G, HUANG J, et al.Elucidation of a universal size-control mechanism in Drosophila and mammals[J].Cell, 2007, 130 (6) :1120-1133.

[25]ZHAO B, YE X, YU J, et al.TEAD mediates YAP-dependent gene induction and growth control[J].Genes Dev, 2008, 22:1962-1971.

[26]HEN L, LOH PG, SONG H.Structural and functional insights into the TEAD-YAP complex in the Hippo signaling pathway[J].Protein Cell, 2010, 1 (12) :1073-1083.

[27]VISSERGRIEVE S, ZHOU Z, SHE YM, et al.LATS1 tumor suppressor is a novel actin-binding protein and negative regulator of actin polymerization[J].Cell Res, 2011, 21 (10) :1513-1516.

[28] DONG J, FELDMANN G, HUANG J, et al.Elucidation of a universal size-control mechanism in Drosophila and mammals[J].Cell, 2007, 130 (6) :1120-1123.

施引文献

资源附件(0)

访问统计