Oncotarget

Priority Research Papers:

Specific micro-RNA expression patterns distinguish the basal and luminal subtypes of muscle-invasive bladder cancer

Andrea E. Ochoa, Woonyoung Choi, Xiaoping Su, Arlene Siefker-Radtke, Bogdan Czerniak, Colin Dinney and David J. McConkey _

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Oncotarget. 2016; 7:80164-80174. https://doi.org/10.18632/oncotarget.13284

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Abstract

Andrea E. Ochoa1,2, 6, Woonyoung Choi1,2, Xiaoping Su3, Arlene Siefker-Radtke5, Bogdan Czerniak4, Colin Dinney1 and David J. McConkey1,2,6,7,8

1 Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

2 Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

3 Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

4 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

5 Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

6 Program in Experimental Therapeutics, University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA

7 Program in Cancer Biology, University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA

8 Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA

Correspondence to:

David J. McConkey, email:

Keywords: urothelial cancer, TCGA, consensus clustering, PPARG, EMT

Received: August 01, 2016 Accepted: October 12, 2016 Published: November 10, 2016

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.


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