Assessment of prognostic implication of a panel of oncogenes in bladder cancer and identification of a 3-gene signature associated with recurrence and progression risk in non-muscle-invasive bladder cancer

Constance Le Goux (1, 2) , Sophie Vacher (1) , Anne Schnitzler (1) , Nicolas Barry Delongchamps (3) , Marc Zerbib (3) , Michael Peyromaure (3) , Mathilde Sibony (4) , Yves Allory (1) , Ivan Bieche (1, 5) , Diane Damotte (4, 6) , Geraldine Pignot (7)

1 Institut Curie [Paris]
2 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
3 Service d'urologie [CHU Cochin]
4 Hôpital Cochin [AP-HP]
5 IC UM3 (UMR 8104 / U1016) - Institut Cochin
6 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
7 IPC - Institut Paoli-Calmettes

This study evaluated the prognostic value of a panel of 29 oncogenes derived from the analysis of The Cancer Genome Atlas (TCGA data) or from the recent literature on bladder tumors on a well-characterized series of muscle-invasive bladder cancer (MIBC) and non-MIBC (NMIBC) samples and tried to identify molecular prognostic markers. Mutations of HRAS, FGFR3, PIK3CA and TERT were found in 2.9%, 27.2%, 14.9% and 76.7% of tumor samples, respectively. Concerning NMIBC, on multivariate analysis, RXRA and FGFR3 levels were associated with recurrence-free survival (RFS) (p = 0.0022 and p = 0.0069) and RXRA level was associated with progression to muscle-invasive disease (p = 0.0068). We identified a 3-gene molecular signature associated with NMIBC prognosis. FGFR3 overexpression was associated with reduced response to Bacillus Calmette-Guerin treatment (p = 0.037). As regards MIBC, on multivariate analysis, ERCC2 overexpression was associated with RFS (p = 0.0011) and E2F3 and EGFR overexpression were associated with overall survival (p = 0.014 and p = 0.035). RT-PCR findings were confirmed by IHC for FGFR3. Genomic alterations in MIBC revealed in TCGA data also concern NMIBC and seem to be associated with prognosis in terms of recurrence and progression. Correcting these alterations by targeted therapies seems a promising pharmacological approach.

Domaines: Cancer; Urologie et Néphrologie; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Constance Le Goux, Sophie Vacher, Anne Schnitzler, Nicolas Barry Delongchamps, Marc Zerbib, et al.. Assessment of prognostic implication of a panel of oncogenes in bladder cancer and identification of a 3-gene signature associated with recurrence and progression risk in non-muscle-invasive bladder cancer. Scientific Reports, 2020, 10 (1), pp.16641. ⟨10.1038/s41598-020-73642-8⟩. ⟨hal-02986867⟩