title: Independent component analysis uncovers the landscape of the bladder tumor transcriptome and reveals insights into luminal and basal subtypes.
abstract: 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.
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; INSERM, U900, 75248 cedex 05 Paris, France; Ecole des Mines ParisTech, 77305 cedex Fontainebleau, France; CNRS, UMR 144, Oncologie Moléculaire, Equipe Labellisée Ligue Contre le Cancer, Institut Curie, 75248 cedex 05 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Biton
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; CNRS, UMR 144, Oncologie Moléculaire, Equipe Labellisée Ligue Contre le Cancer, Institut Curie, 75248 cedex 05 Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bernard-Pierrot
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; CNRS, UMR 144, Oncologie Moléculaire, Equipe Labellisée Ligue Contre le Cancer, Institut Curie, 75248 cedex 05 Paris, France.
authors.forename: Yinjun
authors.initials: Y
authors.lastname: Lou
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; CNRS, UMR 144, Oncologie Moléculaire, Equipe Labellisée Ligue Contre le Cancer, Institut Curie, 75248 cedex 05 Paris, France.
authors.forename: Clémentine
authors.initials: C
authors.lastname: Krucker
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; CNRS, UMR 144, Oncologie Moléculaire, Equipe Labellisée Ligue Contre le Cancer, Institut Curie, 75248 cedex 05 Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Chapeaublanc
authors.affiliation: Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
authors.forename: Carlota
authors.initials: C
authors.lastname: Rubio-Pérez
authors.affiliation: Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), 08003 Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: López-Bigas
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; CNRS, UMR 144, Oncologie Moléculaire, Equipe Labellisée Ligue Contre le Cancer, Institut Curie, 75248 cedex 05 Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Kamoun
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; CNRS, UMR 144, Oncologie Moléculaire, Equipe Labellisée Ligue Contre le Cancer, Institut Curie, 75248 cedex 05 Paris, France; Service d'Urologie, Hôpital Foch, 92150 Suresnes, France; Université de Versailles - Saint-Quentin-en-Yvelines, Faculté de Médecine Paris - Ile-de-France Ouest, 78280 Guyancourt, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Neuzillet
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; INSERM, U900, 75248 cedex 05 Paris, France; Ecole des Mines ParisTech, 77305 cedex Fontainebleau, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gestraud
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; INSERM, U900, 75248 cedex 05 Paris, France; Ecole des Mines ParisTech, 77305 cedex Fontainebleau, France.
authors.forename: Luca
authors.initials: L
authors.lastname: Grieco
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; CNRS, UMR 144, Oncologie Moléculaire, Equipe Labellisée Ligue Contre le Cancer, Institut Curie, 75248 cedex 05 Paris, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rebouissou
authors.affiliation: Ligue Nationale Contre le Cancer, Cartes d'Identité des Tumeurs Program, 75013 Paris, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: de Reyniès
authors.affiliation: CNRS, UMR 8200, Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France; INSERM, U946, 75010 Paris, France.
authors.forename: Simone
authors.initials: S
authors.lastname: Benhamou
authors.affiliation: Service d'Urologie, Hôpital Foch, 92150 Suresnes, France; Université de Versailles - Saint-Quentin-en-Yvelines, Faculté de Médecine Paris - Ile-de-France Ouest, 78280 Guyancourt, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lebret
authors.affiliation: Jack Birch Unit of Molecular Carcinogenesis, Department of Biology, University of York, York Y010 5DD, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Southgate
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; INSERM, U900, 75248 cedex 05 Paris, France; Ecole des Mines ParisTech, 77305 cedex Fontainebleau, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
authors.affiliation: AP-HP, Département de Pathologie, Hôpitaux Universitaires Henri Mondor, 94000 Créteil, France; INSERM, U955, 94000 Créteil, France; Université Paris-Est, Faculté de Médecine, 94000 Créteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allory
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; INSERM, U900, 75248 cedex 05 Paris, France; Ecole des Mines ParisTech, 77305 cedex Fontainebleau, France.
authors.forename: Andrei
authors.initials: A
authors.lastname: Zinovyev
authors.affiliation: Institut Curie, Centre de Recherche, 75248 cedex 05 Paris, France; CNRS, UMR 144, Oncologie Moléculaire, Equipe Labellisée Ligue Contre le Cancer, Institut Curie, 75248 cedex 05 Paris, France. Electronic address: francois.radvanyi@curie.fr.
authors.forename: François
authors.initials: F
authors.lastname: Radvanyi
mesh_terms: D000465:Algorithms; D063646:Carcinogenesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D030541:Databases, Genetic; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D009132:Muscles / Q000473:pathology; D009361:Neoplasm Invasiveness; D047495:PPAR gamma / Q000378:metabolism; D015203:Reproducibility of Results; D059467:Transcriptome / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D019459:Urothelium / Q000473:pathology
chemical_list: D047495:PPAR gamma