期刊论文详细信息
Diagnostic Pathology
Prognostic impact of TAZ and β-catenin expression in adenocarcinoma of the esophagogastric junction
Jianping Zhang4  Zhongmei Zhao1  Lei Qi5  Wenna Shi2  Fei Chen3  Lidan Sun4 
[1] Department of Gynecology and Obstetrics, Laiyang City Centre Hospital, Laiyang, Shandong 265200, People's Republic of China;Department of Gastroenterology, Qilu Hospital, Shandong University, 107#,Wenhua Xi Road, Jinan, Shandong 250012, People's Republic of China;Department of Pathology, Shandong University School of Medicine, 44#,Wenhua Xi Road, Jinan, Shandong 250012, People's Republic of China;Department of Pathology, Qilu Hospital, Shandong University, 107#,Wenhua Xi Road, Jinan, Shandong 250012, People's Republic of China;Department of Orthopedics, Qilu Hospital, Shandong University, 107#,Wenhua Xi Road, Jinan, Shandong 250012, People's Republic of China
关键词: Immunohistochemistry;    Prognosis;    Esophagogastric junction;    Adenocarcinoma of the esophagogastric junction;    Correlation;    β-catenin;    TAZ;   
Others  :  870261
DOI  :  10.1186/1746-1596-9-125
 received in 2014-04-23, accepted in 2014-06-22,  发布年份 2014
PDF
【 摘 要 】

Background

TAZ is a downstream agent of Hippo signal pathway. β-catenin is a cell adhesion molecule associated with the invasion and metastasis of carcinomas as well as a critical component of Wnt pathway. TAZ and β-catenin have long been thought to play a vital role in tumour development and progression. This study aimed to detect expression of TAZ and β-catenin in adenocarcinoma of the esophagogastric junction (AEG) and explore their clinicopathological significance.

Methods

The expression of TAZ and β-catenin were detected by immunohistochemistry of 135 AEG samples, and analyzed with complete clinicopathological features. Overall survival rates were also calculated using the Kaplan-Meier method. Cox proportional hazard model was performed to assess the prognostic values. 37 normal mucosa and 41 dysplasia samples of esophagogastric junction (EGJ) were studied comparably.

Results

TAZ protein showed a strictly nuclear staining pattern in AEG and dysplasia with IHC. Expression of TAZ was higher in dysplasia and AEG compared with normal mucosa (P < 0.001, 0.008). The positive expression rate of nuclear β-catenin was significantly higher in carcinoma and dysplasia than that in normal mucosa (P < 0.001, =0.046). Abnormal expression rate of membranous β-catenin in AEG was significantly higher than that in normal mucosa tissues and dysplasia (P = 0.001, 0.002). In AEG, over expression of TAZ was directly correlated with abnormal nuclear β-catenin expression (r = 0.298, P < 0.001) and membranous β-catenin (r = 0.202, P = 0.019). Patients with abnormal TAZ or β-catenin expression of AEG exhibited a shorter overall survival (OS) and lower overall survival rate than those with normal TAZ or β-catenin expression (P < 0.05). In addition, patients with abnormal expression of both TAZ and β-catenin exhibited worst overall survival. In multivariate survival analysis, abnormal expression of TAZ, TAZ & β-catenin (nuclear and membranous) and tumour differentiation were found to be independent prognostic factors related to OS of AEG patients.

Conclusions

Over expression of TAZ was associated with abnormal expression of β-catenin, which is correlated with poor prognosis of patients with AEG. Abnormal expression of TAZ and TAZ & β-catenin (nuclear and membranous) are independent prognostic factors, so targeting TAZ and β-catenin could prove to be a promising therapeutic strategy for the treatment of AEG.

【 授权许可】

   
2014 Sun et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140730080346265.pdf 1185KB PDF download
66KB Image download
112KB Image download
160KB Image download
【 图 表 】

【 参考文献 】
  • [1]Siewert JR, Stein HJ: Adenocarcinoma of the gastresopha-geal junction: classifiction, pathology and extent of resection. Dis Esoph 1996, 9:173-182.
  • [2]Oda I, Abe S, Kusano C, Suzuki H, Nonaka S, Yoshinaga S, Taniguchi H, Shimoda T, Gotoda T: Correlation between endoscopic macroscopic type and invasion depth for early esophagogastric junction adenocarcinomas. Gastric Cancer 2011, 14:22-27.
  • [3]Abdi-Rad A, Ghaderi-sohi S, Nadimi-Barfroosh H, Emami S: Trend in incidence of gastric adenocarcinoma by tumour location from 1969–2004: a study in one referral center in Iran. Diagn Pathol 2006, 1:5. BioMed Central Full Text
  • [4]Warneke VS, Behrens HM, Hartmann JT, Held H, Becker T, Schwarz NT, Röcken C: Cohort study based on the seventh edition of the TNM classification for gastric cancer: proposal of a new staging system. J Clin Oncol 2011, 29:2364-2371.
  • [5]Feith M, Stein HJ, Siewert JR: Adenocarcinoma of the esophagogastric junction: surgical therapy based on 1602 consecutive resected patients. Surg Oncol Clin N Am 2006, 15:751-764.
  • [6]Hosokawa Y, Kinoshita T, Konishi M, Takahashi S, Gotohda N, Kato Y, Daiko H, Nishimura M, Katsumata K, Sugiyama Y, Kinoshita T: Clinicopathological features and prognostic factors of adenocarcinoma of the esophagogastric junction according to Siewert classification: experiences at a single institution in Japan. Ann Surg Oncol 2012, 19:677-683.
  • [7]Kanai F, Marignani PA, Sarbassova D, Yagi R, Hall RA, Donowitz M, Hisaminato A, Fujiwara T, Ito Y, Cantley LC, Yaffe MB: TAZ: a novel transcriptional co-activator regulated by interactions with14-3-3 and PDZ domain proteins. EMBO J 2000, 19:6778-6791.
  • [8]Zhang L, Yue T, Jiang J: Hippo signaling pathway and organ size control. Fly (Austin) 2009, 3:68-73.
  • [9]Zhao B, Lei QY, Guan KL: The Hippo-YAP path-way: new connections between regulation of organ size and cancer. Curr Opin Cell Biol 2008, 20:638-646.
  • [10]Wu S, Huang J, Dong J, Pan D: Hippo encodes a Ste-20 family protein kinase that restricts cell proliferationand promotes apoptosis in conjunction with salvador and warts. Cell 2003, 114:445-456.
  • [11]Justice RW, Zilian O, Woods DF, Noll M, Bryant PJ: The Drosophila tumour suppressor gene warts encodes a homolog of humanmyotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev 1995, 9:534-546.
  • [12]Kango-Singh M, Nolo R, Tao C, Verstreken P, Hiesinger PR, Bellen HJ, Halder G: Shar-pei mediates cell proliferation arrest during imaginal disc growth inDrosophila. Development 2002, 129:5719-5730.
  • [13]Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA, Gayyed MF, Anders RA, Maitra A, Pan D: Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 2007, 130:1120-1133.
  • [14]Cui CB, Cooper LF, Yang X, Karsenty G, Aukhil I: Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ. Mol Cell Biol 2003, 23:1004-1013.
  • [15]Murakami M, Tominaga J, Makita R, Uchijima Y, Kurihara Y, Nakagawa O, Asano T, Kurihara H: Transcriptional activity of Pax3 is co-activated by TAZ. Biochem Biophys Res Commun 2006, 339:533-539.
  • [16]Mahoney WM Jr, Hong JH, Yaffe MB, Farrance IK: The transcriptional co-activator TAZ interacts differentially withtranscriptional enhancer factor-1 (TEF-1) family members. Biochem J 2005, 388:217-225.
  • [17]Hong JH, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R, Mueller E, Benjamin T, Spiegelman BM, Sharp PA, Hopkins N, Yaffe MB: TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science 2005, 309:1074-1078.
  • [18]Hong JH, Yaffe MB: TAZ: a beta-catenin-like molecule that regulates mesenchymal stem cell differentiation. Cell Cycle 2006, 5:176-179.
  • [19]Murakami M, Nakagawa M, Olson EN, Nakagawa O: A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome. Proc Natl Acad Sci U S A 2005, 102:18034-18039.
  • [20]McCrea PD, Gumbiner BM: Purification of a 92-kDa cytoplasmic protein tightly associated with the cell-cell adhesion molecule E-cadherin (uvomorulin). Characterization and extractability of the protein complex from the cell cytostructure. J Biol Chem 1991, 266:4514-4520.
  • [21]Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P: Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 1997, 275:1790-1792.
  • [22]Munemitsu S, Albert I, Souza B, Rubinfeld B, Polakis P: Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumour-suppressor protein. Proc Natl Acad Sci U S A 1995, 92:3046-3050.
  • [23]Orford K, Crockett C, Jensen JP, Weissman AM, Byers SW: Serine phosphorylation-regulated ubiquitination and degradation of beta-catenin. J Biol Chem 1997, 272:24735-24738.
  • [24]Bienz M, Clevers H: Linking colorectal cancer to Wnt signaling. Cell 2000, 103:311-320.
  • [25]Iwao K, Nakamori S, Kameyama M, Imaoka S, Kinoshita M, Fukui T, Ishiguro S, Nakamura Y, Miyoshi Y: Activation of the beta-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations. Cancer Res 1998, 58:1021-1026.
  • [26]Osterheld MC, Bian YS, Bosman FT, Benhattar J, Fontolliet C: Beta-catenin expression and its association with prognostic factors in adenocarcinoma developed in Barrett esophagus. Am J Clin Pathol 2002, 117:451-456.
  • [27]Kim HS, Hong EK, Park SY, Kim WH, Lee HS: Expression of beta-catenin and E-cadherin in the adenoma-carcinoma sequence of the stomach. Anticancer Res 2003, 23:2863-2868.
  • [28]Varelas X, Miller BW, SoPko R, Song S, Gregorieff A, Fellouse FA, Sakuma R, Pawson T, Hunziker W, McNeill H, Wrana JL, Attisano L: The Hippo pathway regulates Wnt/beta-catenin signaling. Dev Cell 2010, 18:579-591.
  • [29]Azzolin L, Zanconato F, Bresolin S, Forcato M, Basso G, Bicciato S, Cordenonsi M, Piccolo S: Role of TAZ as mediator of Wnt signaling. Cell 2012, 151:1443-1456.
  • [30]Tsai BP, Hoverter NP, Waterman ML: Blending hippo and WNT: sharing messengers and regulation. Cell 2012, 151:1401-1403.
  • [31]Imajo M, Miyatake K, Iimura A, Miyamoto A, Nishida E: A molecular mechanism that links Hippo sig-nalling to the inhibition of Wnt/β-catenin signalling. EMBO J 2012, 31:1109-1122.
  • [32]Woo DK, Kim HS, Lee HS, Kang YH, Yang HK, Kim WH: Altered expression and mutation of beta-catenin gene in gastric carcinomas and cell lines. Int J Cancer 2001, 95:108-113.
  • [33]Shan L, Ying J, Lu N: HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population. Diagn Pathol 2013, 8:76. BioMed Central Full Text
  • [34]Hasegawa S, Yoshikawa T: Adenocarcinoma of the esophagogastric junction: incidence, characteristics, and treatment strategies. Gastric Cancer 2010, 13:63-73.
  • [35]Meimarakis G, Winter H, Assmann I, Kopp R, Lehn N, Kist M, Stolte M, Jauch KW, Hatz RA: Helicobacter pylori as a prognostic indicator after curative resection of gastric carcinoma: a prospective study. Lancet Oncol 2006, 7:211-222.
  • [36]Marrelli D, Pedrazzani C, Berardi A, Corso G, Neri A, Garosi L, Vindigni C, Santucci A, Figura N, Roviello F: Negative Helicobacter pylori status is associated with poor prognosis in patients with gastric cancer. Cancer 2009, 115:2071-2080.
  • [37]Hundahl SA, Phillips JL, Menck HR: The National cancer Data Base Report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: fifth edition American Joint Committee on Cancer staging, proximal disease, and the “different disease” hypothesis. Cancer 2000, 88:921-932.
  • [38]Hasegawa S, Yoshikawa T, Cho H, Tsuburaya A, Kobayashi O: Is adenocarcinoma of the esophagogastric junction different between Japanand western countries? The incidence and clinicopathological features at aJapanese high-volume cancer center. World J Surg 2009, 33:95-103.
  • [39]Hongxia C, Hui L, Yejun Q, Ying L: Nuclear beta-catenin overexpression in metastatic sentinel lymph node is associated with synchronous liver metastasis in colorectal cancer. Diagn Pathol 2011, 6:109. BioMed Central Full Text
  • [40]Leers JM, DeMeester SR, Chan N, Ayazi S, Oezcelik A, Abate E, Banki F, Lipham JC, Hagen JA, DeMeester TR: Clinical characteristics, biologic behavior, and survival after esophagectomyare similar for adenocarcinoma of the gastroesophageal junction and thedistal esophagus. J Thorac Cardiovasc Surg 2009, 138:594-602.
  • [41]Jeong GO, Shin SH, Seo EJ, Kwon YW, Heo SC, Kim KH, Yoon MS, Suh DS, Kim JH: TAZ mediates lysophosphatidic acid-induced migration and proliferation of epithelial ovarian cancer cells. Cell Physiol Biochem 2013, 32:253-263.
  • [42]Wang L, Shi S, Guo Z, Zhang X, Han S, Yang A, Wen W, Zhu Q: Overexpression of YAP and TAZ is an independent predictor of prognosis in colorectal cancer and related to the proliferation and metastasis of colon cancer cells. PLoS One 2013, 8:e65539.
  • [43]Lei QY, Zhang H, Zhao B, Zha ZY, Bai F, Pei XH, Zhao S, Xiong Y, Guan KL: TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippopathway. Mol Cell Biol 2008, 28:2426-2436.
  • [44]Zhao D, Zhi X, Zhou Z, Chen C: TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumourigenesis. Carcinogenesis 2012, 33:59-67.
  • [45]Yang N, Morrison CD, Liu P, Miecznikowski J, Bshara W, Han S, Zhu Q, Omilian AR, Li X, Zhang J: TAZ induces growth factor-independent proliferation through activation of EGFR ligand amphiregulin. Cell Cycle 2012, 11:2922-2930.
  • [46]Mao TL, Chu JS, Jeng YM, Lai PL, Hsu HC: Expression of mutant nuclear beta-catenin correlates with non-invasive hepatocellular carcinoma, absence of portal vein spread, and good prognosis. J Pathol 2001, 193:95-101.
  文献评价指标  
  下载次数:34次 浏览次数:30次