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

TY - JOUR

T1 - Independent Component Analysis Uncovers the Landscape of the Bladder Tumor Transcriptome and Reveals Insights into Luminal and Basal Subtypes

AU - Biton, Anne

AU - Bernard-Pierrot, Isabelle

AU - Lou, Yinjun

AU - Krucker, Clémentine

AU - Chapeaublanc, Elodie

AU - Rubio-Pérez, Carlota

AU - López-Bigas, Nuria

AU - Kamoun, Aurélie

AU - Neuzillet, Yann

AU - Gestraud, Pierre

AU - Grieco, Luca

AU - Rebouissou, Sandra

AU - deReyniès, Aurélien

AU - Benhamou, Simone

AU - Lebret, Thierry

AU - Southgate, Jennifer

AU - Barillot, Emmanuel

AU - Allory, Yves

AU - Zinovyev, Andrei

AU - Radvanyi, François

PY - 2014/11/20

Y1 - 2014/11/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84912071423&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2014.10.035

DO - 10.1016/j.celrep.2014.10.035

M3 - Article

AN - SCOPUS:84912071423

VL - 9

SP - 1235

EP - 1245

JO - Cell reports

JF - Cell reports

SN - 2211-1247

IS - 4

ER -