Institut Curie


The web supplement to
Anne Biton et al. 2014

 Logo_inserm
Logo_cnrs
Independent component analysis uncovers the landscape of the bladder tumor transcriptome and reveals new insights into luminal and basal subtypes
Anne Biton1,2,3,4,16,19, Isabelle Bernard-Pierrot1,4,19, Yinjun Lou1,4,17, Clémentine Krucker1,4, Elodie Chapeaublanc1,4, Carlota Rubio-Perez5, Nuria Lopez-Bigas5,6, Aurélie Kamoun1,4, Yann Neuzillet1,4,7,8, Pierre Gestraud1,2,3, Luca Grieco1,2,3, Sandra Rebouissou1,4,18, Aurélien de Reyniès9, Simone Benhamou10,11, Thierry Lebret7,8, Jennifer Southgate12, Emmanuel Barillot1,2,3, Yves Allory13,14,15, Andrei Zinovyev1,2,3,20, François Radvanyi1,4,20*

1 Institut Curie, Centre de Recherche, 75248 cedex 05, Paris, France. 2 INSERM U900, 75248 cedex 05, Paris, France. 3 Ecole des Mines ParisTech, 77305 cedex, Fontainebleau, France. 4 CNRS, UMR 144, Oncologie Moléculaire, Equipe Labellisée Ligue Contre le Cancer, Institut Curie, 75248 cedex 05, Paris, France. 5 Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003, Barcelona, Spain 6 Catalan Institution for Research and Advanced Studies (ICREA), 08003 Barcelona, Spain 7 Service d'Urologie, Hopital Foch, 92150 Suresnes, France. 8 Université de Versailles - Saint-Quentin-en-Yvelines, Faculté de Médecine Paris - Ile-de-France Ouest, 78280 Guyancourt, France. 9 Ligue Nationale Contre le Cancer, Cartes d'Identité des Tumeurs program, 75013 Paris, France. 10 CNRS, UMR 8200, Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France. 11 INSERM, U946, 75010 Paris, France. 12 Jack Birch Unit of Molecular Carcinogenesis, Department of Biology, University of York, York Y010 5DD, United Kingdom. 13 AP-HP, Hopitaux Universitaires Henri Mondor, Département de Pathologie, 94000 Créteil, France. 14 INSERM, Unité 955, 94000 Créteil, France. 15 Université Paris-Est, Faculté de Médecine, 94000 Créteil, France. 16 Present address: Department of Medicine, Lung Biology Center, University of California San Francisco, San Francisco, CA 94143-2922, USA. 17 Present address: ZheJiang University, Institute of Hematology, HangZhou, ZheJiang 310058, China. 18 Present address: INSERM, UMR-674, Génomique Fonctionnelle des Tumeurs Solides, IUH, 75010 Paris, France. 19 Co-first author 20 Co-senior author *Corresponding author: François Radvanyi, phone: +33-1-56-24-63-39, francois.radvanyi@curie.fr




Summary

Extracting relevant information from large-scale data offers unprecedented opportunities in cancerology. We applied independent component analysis (ICA) to bladder cancer transcriptome datasets and interpreted the components using gene enrichment analysis and molecular, clinico- pathological, and processing data associated with the tumors. We identified components/biological processes associated with the tumor cells or tumor microenvironment and components due to technical biases. Applying ICA to nine cancer types allowed the identification of 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. The 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 datasets.

Download data:
 
Images TMA ICA (png) Get it (.zip 614.4 MB)
 
Images TMA ICA (pdf) Get it (.zip 6.8 GB)


Last modified August 14 2014 11:23:39