title: Identification of a three-gene expression signature of early recurrence in non-muscle-invasive urothelial cell carcinoma of the bladder.
abstract: OBJECTIVE
  To identify the expression profile of early recurring non-muscle-invasive bladder cancer (NMI-BC).
  
  
  METHODS
  We selected primary NMI-BC according to the following criteria: complete resection, primary occurrence of urothelial cell carcinoma, stage cTa or T1, low grade, no carcinoma in situ. All patients underwent a transurethral resection of the bladder and were followed according to the Guidelines of European Association of Urology. Expression of 110 target genes was studied by using real time quantitative RT-PCR. The correlation between the absolute expression and early recurrence was analyzed by using a Cox regression model. The ability of a gene to distinguish the tumors with early recurrence from those with late recurrence was determined by using a ROC-AUC test. A hierarchical classification was established by using the software of GeneANOVA and tested by a χ(2) test.
  
  
  RESULTS
  Forty-seven tumors were studied: 25 with early recurrence vs. 22 with late or null recurrence. These 2 groups of tumors have a significantly different expression profile in 3 genes among the 110-gene expression profile: peroxysome proliferator-activated receptor-γ (PPARG) (P = 0.031), stathmin-1 (STMN1) (P = 0.041), Caveolin-2 (CAV2) (P = 0.004). The combination of the expression of these 3 genes was significantly predictive for early recurrence leading to a correct hierarchical classification of the NMI-BC regarding the time-to-recurrence (P < 0.001).
  
  
  CONCLUSIONS
  This study identifies a concise 3-gene panel that is associated with time to recurrence. This 3-gene signature has to be confirmed in a prospective study and in larger cohort of patients. However, our preliminary results are promising and gene expression profiling seems to be an interesting approach in cTa-T1 tumors for recurrence prediction.
authors.affiliation: Urology Department, Saint-Louis Hospital, Assistance publique - Hôpitaux de Paris, Paris VII University, Paris, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Dubosq
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ploussard
authors.forename: Hany
authors.initials: H
authors.lastname: Soliman
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Turpin
authors.forename: Alain
authors.initials: A
authors.lastname: Latil
authors.forename: François
authors.initials: F
authors.lastname: Desgrandchamps
authors.forename: Hugues
authors.initials: H
authors.lastname: de The
authors.forename: Pierre
authors.initials: P
authors.lastname: Mongiat-Artus
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D051243:Caveolin 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D047495:PPAR gamma / Q000235:genetics*; D016016:Proportional Hazards Models; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050777:Stathmin / Q000235:genetics*; D059467:Transcriptome; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D051243:Caveolin 2; D047495:PPAR gamma; C493995:STMN1 protein, human; D050777:Stathmin