Identification of a three-gene expression signature of early recurrence in non-muscle-invasive urothelial cell carcinoma of the bladder.

Objectives: To identify the expression profile of early recurring non-muscle-invasive bladder cancer (NMI-BC).

Materials And 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.