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Cell Rep. 2014 Nov 20;9(4):1235-45. doi: 10.1016/j.celrep.2014.10.035. Epub 2014 Nov 13.

Independent component analysis uncovers the landscape of the bladder tumor transcriptome and reveals insights into luminal and basal subtypes.

Author information

1
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.
2
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.
3
Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
4
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.
5
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.
6
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.
7
Ligue Nationale Contre le Cancer, Cartes d'Identité des Tumeurs Program, 75013 Paris, France.
8
CNRS, UMR 8200, Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France; INSERM, U946, 75010 Paris, France.
9
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.
10
Jack Birch Unit of Molecular Carcinogenesis, Department of Biology, University of York, York Y010 5DD, UK.
11
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.
12
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.

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.

PMID:
25456126
DOI:
10.1016/j.celrep.2014.10.035
[Indexed for MEDLINE]
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