title: Protein expression of ZEB2 in renal cell carcinoma and its prognostic significance in patient survival.
abstract: BACKGROUND
  ZEB2 has been reportedly shown to mediate the epithelial-to-mesenchymal transition (EMT) and disease aggressiveness in human tumors. However, the expression status of ZEB2 in renal cell carcinoma (RCC) and ZEB2's clinicopathologic/prognostic significance are poorly understood.
  
  
  RESULTS
  In this study, tissue microarray, immunohistochemistry (IHC) and western blot analyses were utilized to investigate the ZEB2 expression status in RCC and adjacent renal tissue samples. In our study, samples from 116 RCC patients treated with radical nephrectomy were used as a training set to generate a ZEB2 optimal cut-point for patient outcome by receiver operating characteristic (ROC) analysis. For validation, the correlation of ZEB2 expression with the clinical characteristics and patient outcomes in another set (including 113 patients) was analyzed to validate the obtained cut-point. In the training and validation sets, high expression of ZEB2, defined by ROC analysis, predicted a poorer overall survival and progression-free survival, as evidenced by the univariate and multivariate analyses. In different subsets of overall patients, ZEB2 expression was also a prognostic indicator in patients with stage I/II, stage III/IV, grade 1/2 and grade 3/4 disease (P<0.05). Downregulation of ZEB2 by shRNA decreased the migration and invasion ability of 769-P cells in vitro. Furthermore, high ZEB2 expression was positively correlated with vimentin expression and inversely linked to E-cadherin expression in RCC.
  
  
  CONCLUSIONS
  Our findings provide a basis for the concept that high ZEB2 expression in RCC may be important in the acquisition of an aggressive phenotype. This evidence suggests that ZEB2 overexpression (examined by IHC) is an independent biomarker for the poor prognosis of patients with RCC.
authors: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Yong
authors: Y
authors: Fang
authors: Jinhuan
authors: J
authors: Wei
authors: Jiazheng
authors: J
authors: Cao
authors: Hongwei
authors: H
authors: Zhao
authors: Bing
authors: B
authors: Liao
authors: Shaopeng
authors: S
authors: Qiu
authors: Daohu
authors: D
authors: Wang
authors: Junhang
authors: J
authors: Luo
authors: Wei
authors: W
authors: Chen
mesh_terms: D014408:Biomarkers, Tumor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D016019:Survival Analysis; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2
references: CA Cancer J Clin. 2011 Jul-Aug;61(4):212-36
references: 21685461
references: Cell. 2008 May 16;133(4):704-15
references: 18485877
references: Int J Oncol. 2005 Dec;27(6):1535-41
references: 16273209
references: J Clin Oncol. 2006 Dec 10;24(35):5565-75
references: 17158542
references: Oncogene. 2006 Aug 17;25(36):4975-85
references: 16568083
references: J Biol Chem. 1999 Jul 16;274(29):20489-98
references: 10400677
references: Nat Cell Biol. 2008 May;10(5):593-601
references: 18376396
references: Exp Mol Pathol. 2010 Oct;89(2):182-9
references: 20515682
references: Br J Cancer. 2004 Mar 22;90(6):1265-73
references: 15026811
references: Cell Signal. 2005 May;17(5):535-47
references: 15683729
references: Cancer. 2005 Apr 15;103(8):1631-43
references: 15742334
references: Cancer Res. 2006 Mar 1;66(5):2725-31
references: 16510593
references: Ann Surg Oncol. 2012 Feb;19(2):612-9
references: 21913013
references: Nat Rev Cancer. 2007 Jun;7(6):415-28
references: 17508028
references: Oncogene. 2007 Apr 5;26(16):2381-5
references: 17043655
references: PLoS One. 2012;7(2):e32838
references: 22393452
references: J Urol. 2011 Jun;185(6):2035-9
references: 21496854
references: Genes Dev. 2008 Mar 15;22(6):756-69
references: 18347095
references: Mol Cell. 2001 Jun;7(6):1267-78
references: 11430829
references: J Biol Chem. 2003 Jul 11;278(28):26135-45
references: 12714599
references: Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14884-9
references: 19706487
references: Mol Med. 2011 Jan-Feb;17(1-2):12-20
references: 20844838
references: EMBO J. 1999 Sep 15;18(18):5073-84
references: 10487759
references: Dev Cell. 2008 Jun;14(6):818-29
references: 18539112
references: Genes Dev. 2008 Apr 1;22(7):894-907
references: 18381893
references: BJU Int. 2012 Dec;110(11 Pt C):E1131-7
references: 22712620
references: Pathologe. 2009 Dec;30 Suppl 2:193-9
references: 19960300
references: Med Mol Morphol. 2009 Jun;42(2):82-91
references: 19536615
references: Cell. 2009 Nov 25;139(5):871-90
references: 19945376
references: IARC Sci Publ. 2008;(160):1-837
references: 19388204
references: RNA. 2007 Aug;13(8):1172-8
references: 17585049
references: EMBO J. 2003 May 15;22(10):2453-62
references: 12743039
references: Cancer Sci. 2010 Jun;101(6):1543-9
references: 20367640
references: Mol Biol Cell. 2007 Nov;18(11):4615-24
references: 17855508
references: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2178-83
references: 16461895
references: Gut. 2011 Jul;60(7):967-76
references: 21330577