Independent Component Analysis Uncovers the Landscape of the Bladder Tumor Transcriptome and Reveals Insights into Luminal and Basal Subtypes

Anne Biton, Isabelle Bernard-Pierrot, Yinjun Lou, Clémentine Krucker, Elodie Chapeaublanc, Carlota Rubio-Pérez, Nuria López-Bigas, Aurélie Kamoun, Yann Neuzillet, Pierre Gestraud, Luca Grieco, Sandra Rebouissou, Aurélien deReyniès, Simone Benhamou, Thierry Lebret, Jennifer Southgate, Emmanuel Barillot, Yves Allory, Andrei Zinovyev, François Radvanyi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 processesoftumor cells or the tumor microenvironment, andother 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.

Original languageEnglish
Pages (from-to)1235-1245
Number of pages11
JournalCell reports
Issue number4
Publication statusPublished - 20 Nov 2014

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