title: Decreased Cezanne expression is associated with the progression and poor prognosis in hepatocellular carcinoma.
abstract: BACKGROUND
  Deubiquitinases, such as CYLD, A20 and Cezanne, have emerged as negative regulators that balance the strength and duration of NF-κB signaling through feedback mechanisms. However, how these serial feedback loops are simultaneously disrupted in cancer remains unclear. The purpose of this study is to investigate the correlation of Cezanne expression with clinicopathological/prognostic value in hepatocellular carcinoma (HCC).
  
  
  METHODS
  The expression levels of Cezanne and matrix metallopeptidase 9 (MMP-9) were assessed by immunohistochemistry in 230 HCC specimens. The correlation between expression of Cezanne and MMP-9, clinicopathological/prognostic value in hepatocellular carcinoma was examined.
  
  
  RESULTS
  Cezanne reduction in HCC was significantly associated with larger tumor, satellite nodule, vascular invasion, TNM stage, BCLC stage and early recurrence. Kaplan-Meier analysis showed that Cezanne was a great predictive factor for overall survival (OS) and time to recurrence (TTR). The expression of Cezanne was decreased in TNM and BCLC stage-dependent manner. In addition, Cezanne reduction was associated with poor prognosis in patients subgroups stratified by tumor size, tumor differentiation, TNM stage and BCLC stage. Moreover, Cezanne was negatively associated with MMP-9 among 230 HCC samples. Patients who had Cezanne downregulation, in which cancer cells showed high invasiveness, had shorter TTR and poor OS. Furthermore, the coindex of Cezanne and preoperative serum AFP levels was significantly correlated with OS and TTR.
  
  
  CONCLUSIONS
  Cezanne has a pivotal role in tumor progression and prognosis, and may act as a potential prognostic biomarker for survival in HCC patients.
authors: Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. wangjh@sysucc.org.cn.
authors: Jia-hong
authors: JH
authors: Wang
authors: Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. weiwei@sysucc.org.cn.
authors: Wei
authors: W
authors: Wei
authors: Department of Ultrasonics, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. guozhx@sysu.org.cn.
authors: Zhi-xing
authors: ZX
authors: Guo
authors: Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. Shiming@sysu.org.cn.
authors: Ming
authors: M
authors: Shi
authors: Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. guorp@sysucc.org.cn.
authors: Rong-ping
authors: RP
authors: Guo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D013997:Time Factors; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000509:alpha-Fetoproteins; D010450:Endopeptidases; C476458:OTUD7B protein, human; D020780:Matrix Metalloproteinase 9
references: J Clin Oncol. 2000 Mar;18(5):1135-49
references: 10694567
references: Genes Dev. 2000 Jan 15;14(2):163-76
references: 10652271
references: J Biol Chem. 2003 Jun 20;278(25):23180-6
references: 12682062
references: Anticancer Res. 2003 Mar-Apr;23(2C):1747-53
references: 12820452
references: Nature. 2004 Aug 5;430(7000):694-9
references: 15258597
references: Hepatology. 1996 Aug;24(2):316-22
references: 8690399
references: Cancer Lett. 2005 Nov 18;229(2):157-69
references: 16125305
references: Ann Surg. 2006 Feb;243(2):229-35
references: 16432356
references: Gastroenterology. 2006 Aug;131(2):461-9
references: 16890600
references: Cell. 2006 Nov 3;127(3):469-80
references: 17081971
references: Cancer Genet Cytogenet. 2007 May;175(1):73-6
references: 17498563
references: Gastroenterology. 2007 Jun;132(7):2557-76
references: 17570226
references: J Clin Oncol. 2007 Jul 20;25(21):3069-75
references: 17634485
references: J Biol Chem. 2008 Mar 14;283(11):7036-45
references: 18178551
references: Cancer Sci. 2008 May;99(5):836-42
references: 18294278
references: Hepatology. 2008 Oct;48(4):1312-27
references: 18821591
references: Oncogene. 2008 Oct 20;27(48):6228-44
references: 18931690
references: Hepatology. 2008 Dec;48(6):2047-63
references: 19003900
references: Gastroenterology. 2008 Dec;135(6):1972-83, 1983.e1-11
references: 18929564
references: Toxicol Lett. 2009 Feb 10;184(3):204-10
references: 19110045
references: CA Cancer J Clin. 2009 Mar-Apr;59(2):111-37
references: 19278961
references: J Hepatol. 2010 Feb;52(2):252-7
references: 20022654
references: Cell Res. 2011 Jan;21(1):159-68
references: 21187858
references: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references: 21296855
references: J Asian Nat Prod Res. 2011 Mar;13(3):242-50
references: 21409686
references: Ann Surg Oncol. 2012 Jul;19 Suppl 3:S375-84
references: 21681378
references: Cell Res. 2013 Feb;23(2):274-89
references: 23247627
references: Clin Cancer Res. 2013 Jun 1;19(11):2810-6
references: 23549874
references: Eur Rev Med Pharmacol Sci. 2013 Jun;17(11):1495-508
references: 23771538
references: Mol Cancer. 2013;12:86
references: 23915189
references: J Hepatol. 2013 Nov;59(5):1037-44
references: 23831118
references: Clin Liver Dis. 2001 Feb;5(1):145-59
references: 11218912