No consensus currently exist on the optimal treatment of patients with high-risk nonmuscle invasive (HGT1) micropapillary variant of bladder cancer (MPBC). Transcripsome analysis may allow stratification of MPBC-HGT1 enabling prediction of recurrence and guide therapeutic management for individual patients. Whole transcriptome RNA-Sequencing of tumors from 23 patients with MPBC-HGT1 and 64 conventional urothelial carcinomas (cUC) (reference set) was performed. Differentially expressed genes between MPBC-HGT1 and cUC-HGT1 were explored. Cox proportional hazard models and Kapplan-Meier methods were used to assess the relation between time to progression (TTP) and individual gene expression adjusting for clinical covariates. Over 3000 genes were differentially expressed in MPBC-HGT1 as compared with cUC-HGT1 and a 26-gene signature is characteristic of MPBC within HGT1. A set of three genes; CD36, FAPB3 and RAETE1; were significantly associated with TTP. High expression of FABP3 and CD36 were associated with shorter TTP (p = 0.045 and p = 0.08) as was low expression of RAET1E (p = 0.01). Our study suggest that a 26-gene signature can define MPBC-HGT1 within conventional urothelial carcinomas. A prognostic risk index of three genes (FABP3, CD36 and RAET1E) was found to be associated with shorter TTP and may help classify a group of patients with MPBC-HGT1 with high-risk of early progression. These observations might have implications in terms of radical cystectomy recommendation in MPBC patients.
Scientific reports. 2020 Nov 18*** epublish ***
Michaela Bowden, Rosa Nadal, Chensheng W Zhou, Lillian Werner, Justine Barletta, Nuria Juanpere, Josep Lloreta, Silvia Hernandez-Llodrà, Juan Morote, Ines de Torres, Anna Orsola, Paloma Cejas, Henry Long, Joaquim Bellmunt
Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, USA. ., Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institutes, National Institutes of Health, Bethesda, MD, USA., Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, USA., Department of Biostatistics, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Department of Pathology, PSMAR-IMIM Research Institute, Barcelona, Spain., Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain., Department of Urology, Hospital Vall D'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain., Department of Pathology, Hospital Vall D'Hebron, Barcelona, Spain., PSMAR-IMIM Research Institute, Barcelona, Spain., Center for Functional Cancer Epigenetics, Dana Farber Cancer Institute, Boston, MA, USA., Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, USA. .