title: Specific micro-RNA expression patterns distinguish the basal and luminal subtypes of muscle-invasive bladder cancer.
abstract: The roles of non-coding RNAs in controlling clinical and biological heterogeneity in bladder cancer remain unclear. We used TCGA's published dataset (n = 405 tumors) as a discovery cohort and created a new validation cohort to define the miRNA expression patterns in the basal and luminal molecular subtypes of muscle-invasive bladder cancer (MIBC). We identified 63 miRNAs by PAM, which optimally identified basal and luminal tumors. The targets of the top luminal miRNAs were activators of EMT (ZEB1, ZEB2) and basal subtype transcription (IL-6, EGFR, STAT3), whereas the targets of the top basal miRNAs were involved in adipogenesis pathways and luminal breast cancer (ERBB2, ERBB3). We also identified a 15-miRNA signature that identified stromally infiltrated basal and luminal MIBCs corresponding to the "cluster IV/immune undifferentiated/claudin-low" and "cluster II/luminal immune" subtypes identified previously, which likely contain samples with higher infiltration rates. Using the 63-miRNA signature, we accurately assigned MIBCs to the basal and luminal subtypes and confirmed that patients with basal tumors had shorter overall survival. The results strongly suggest that miRNAs contribute to the control of the gene expression patterns observed in basal and luminal MIBCs and that they can be used as biomarkers and candidate therapeutic targets.
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Ochoa
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Woonyoung
authors.initials: W
authors.lastname: Choi
authors.affiliation: Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Arlene
authors.initials: A
authors.lastname: Siefker-Radtke
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Czerniak
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Dinney
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Program in Experimental Therapeutics, University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA.|Program in Cancer Biology, University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA.|Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: McConkey
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D019295:Computational Biology; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011379:Prognosis; D015398:Signal Transduction; D059467:Transcriptome; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: EMT; PPARG; TCGA; consensus clustering; urothelial cancer