Extracting relevant information from large-scale data offers unprecedented opportunities in cancerology. We applied independent component analysis (ICA) to bladder cancer transcriptome data sets and interpreted the components using gene enrichment analysis and tumor-associated molecular, clinicopathological, and processing information. We identified components associated with biological processes of tumor cells or the tumor microenvironment, and other components revealed technical biases. Applying ICA to nine cancer types identified cancer-shared and bladder-cancer-specific components. We characterized the luminal and basal-like subtypes of muscle-invasive bladder cancers according to the components identified. The study of the urothelial differentiation component, specific to the luminal subtypes, showed that a molecular urothelial differentiation program was maintained even in those luminal tumors that had lost morphological differentiation. Study of the genomic alterations associated with this component coupled with functional studies revealed a protumorigenic role for PPARG in luminal tumors. Our results support the inclusion of ICA in the exploitation of multiscale data sets.

This work is part of the “Cartes d’Identité des Tumeurs” (CIT) program funded and developed by the “Ligue Nationale contre le Cancer” (LNCC) (http://cit.ligue-cancer.net). We thank E. Voirin, N. Servant, G. Lucotte, and P. Hupé for their help with bioinformatics data management and analysis. We thank members of the bladder cancer CIT consortium (P. Maillé and D. Vordos, Henri Mondor Hospital; M. Sibony, Cochin Hospital; A. Laplanche, IGR, INSERM; Y. Denoux and V. Molinié, Foch Hospital; E. Letouzé, LNCC) for their constant support. This work was supported by the LNCC (to “Oncologie Moléculaire” and “Computational Systems Biology of Cancer” accredited teams), the Institut Curie (to F.R., E.B., A.Z.), the “Centre National de la Recherche Scientifique” (CNRS) (to F.R.), the “Institut National de la Santé et de la Recherche Médicale” (INSERM) (to E.B., A.Z., S.B., and Y.A.), the INCa (INCa_2960 and 4382 to F.R. and Y.A.), ITMO cancer, systems biology program (to A.Z., E.B., and F.R.), the Labex (no. ANR-10-LBX-0038) part of the IDEX PSL (no. ANR-10-IDEX-0001-02 PSL) (to F.R.), and York Against Cancer (to J.S.). A.B. was supported by a grant from the INCa, from the LNCC, and by NIH grant 5U24 CA143799-04 as part of TCGA project, Y.L. by a grant from the “Fondation Franco-Chinoise pour la Science et ses Applications” (FFCSA), Y.N. by a grant from the “Fondation ARC pour la recherche sur le cancer,” and A.K. by a grant from the LNCC