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
SN - 2211-1247
VL - 9
SP - 1235
EP - 1245
JO - Cell reports
JF - Cell reports
IS - 4
ER -