title: Clinical significance of T-bet, GATA-3, and Bcl-6 transcription factor expression in bladder carcinoma.
abstract: The aim of this study was to investigate the clinical significance of three immune cell-related transcription factors, T-bet, GATA-3 and Bcl-6 in bladder cancer in Tunisian patients.
  
  
  
  Expression of T-bet, GATA-3 and Bcl-6 genes was assessed using RT-qPCR in 65 bladder cancers from patients: 32 being diagnosed as low- and medium-grade, 31 as high-grade, 25 as muscle invasive stage and 39 as non-muscle invasive stage. Gene expression was statistically correlated according to the grade, the stage, tobacco consumption, the BCG response and disease severity.
  
  
  
  T-bet levels in patients with high-grade bladder cancer were significantly elevated compared to patients with low- or medium-grade bladder cancer (p = 0.005). In invasive carcinoma (T2-T4), the T-bet levels were significantly higher than in superficial non-invasive bladder tumors (Tis, Ta, and T1) (p = 0.02). However, T-bet is predictive of the response to BCG. Its expression is high in good responders to BCG (p = 0.02). In contrast, the expression of GATA-3 and Bcl-6 in non-invasive carcinoma (p = 0.008 and p = 0.0003) and in patients with low- and medium-grade cancers (p = 0.001 and p < 0.0001) is significantly higher than in invasive bladder tumors and in patients with high-grade bladder carcinoma, respectively. In addition, heavy smokers, whose tumors express low levels of GATA-3 and Bcl-6, are poor responders to BCG (p = 0.01 and p = 0.03). Finally, better patient survival correlated with GATA-3 (p = 0.04) and Bcl-6 (p = 0.04) but not T-bet expression.
  
  
  
  Our results suggest that T-bet expression in bladder tumors could be a positive prognostic indicator of BCG therapy, even if high levels are found in high-grade and stage of the disease. However, GATA-3 and Bcl-6 expression could be considered as predictive factors for good patient survival.
authors.affiliation: Laboratoire d'Immunologie et Immunothérapie des Cancers (LIIC), EPHE, PSL Research University, 75014, Paris, France.|Université Bourgogne Franche-Comté, EA7269, 21000, Dijon, France.|Laboratoire de Génétique, Immunologie et Pathologies Humaines, Faculté de Sciences Tunis, Université de Tunis El Manar, Tunis, Tunisia.
authors.forename: Islem Ben
authors.initials: IB
authors.lastname: Bahria-Sediki
authors.affiliation: Laboratoire d'Immunologie et Immunothérapie des Cancers (LIIC), EPHE, PSL Research University, 75014, Paris, France.|Université Bourgogne Franche-Comté, EA7269, 21000, Dijon, France.
authors.forename: Nadhir
authors.initials: N
authors.lastname: Yousfi
authors.affiliation: Laboratoire d'Immunologie et Immunothérapie des Cancers (LIIC), EPHE, PSL Research University, 75014, Paris, France.|Université Bourgogne Franche-Comté, EA7269, 21000, Dijon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Paul
authors.affiliation: Hôpital Charles Nicolle de Tunis, Tunis, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chebil
authors.affiliation: Hôpital Charles Nicolle de Tunis, Tunis, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Cherif
authors.affiliation: Hôpital Charles Nicolle de Tunis, Tunis, Tunisia.
authors.forename: Rachida
authors.initials: R
authors.lastname: Zermani
authors.affiliation: Laboratoire de Génétique, Immunologie et Pathologies Humaines, Faculté de Sciences Tunis, Université de Tunis El Manar, Tunis, Tunisia.
authors.forename: Amel Ben Ammar
authors.initials: AB
authors.lastname: El Gaaied
authors.affiliation: Laboratoire d'Immunologie et Immunothérapie des Cancers (LIIC), EPHE, PSL Research University, 75014, Paris, France. ali.bettaieb@u-bourgogne.fr.|Université Bourgogne Franche-Comté, EA7269, 21000, Dijon, France. ali.bettaieb@u-bourgogne.fr.|UFR des Sciences de Santé, 7 boulevard Jeanne d'Arc, BP 87900, 21079, Dijon, France. ali.bettaieb@u-bourgogne.fr.
authors.forename: Ali
authors.initials: A
authors.lastname: Bettaieb
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis; D011379:Prognosis; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics* / Q000378:metabolism; D012907:Smoking / Q000235:genetics; D019966:Substance-Related Disorders / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000098815:T-bet Transcription Factor
chemical_list: C084103:BCL6 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D051560:Proto-Oncogene Proteins c-bcl-6; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
keywords: Bcl-6; Bladder carcinomas; GATA-3; Prognosis; T-bet