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Molecular subtypes of urothelial carcinoma are defined by specific gene regulatory systems

Overview of attention for article published in BMC Medical Genomics, May 2015
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Title
Molecular subtypes of urothelial carcinoma are defined by specific gene regulatory systems
Published in
BMC Medical Genomics, May 2015
DOI 10.1186/s12920-015-0101-5
Pubmed ID
Authors

Pontus Eriksson, Mattias Aine, Srinivas Veerla, Fredrik Liedberg, Gottfrid Sjödahl, Mattias Höglund

Abstract

Molecular stratification of bladder cancer has revealed gene signatures differentially expressed across tumor subtypes. While these signatures provide important insights into subtype biology, the transcriptional regulation that governs these signatures is not well characterized. In this study, we use publically available ChIP-Seq data on regulatory factor binding in order to link transcription factors to gene signatures defining molecular subtypes of urothelial carcinoma. We identify PPARG and STAT3, as well as ADIRF, a novel regulator of fatty acid metabolism, as putative mediators of the SCC-like phenotype. We link the PLK1-FOXM1 axis to the rapidly proliferating Genomically Unstable and SCC-like subtypes and show that differentiation programs involving PPARG/RXRA, FOXA1/GATA3 and HOXA/HOXB are differentially expressed in UC molecular subtypes. We show that gene signatures and regulatory systems defined in urothelial carcinoma operate in breast cancer in a subtype specific manner, suggesting similarities at the gene regulatory level of these two tumor types. At the gene regulatory level Urobasal, Genomically Unstable and SCC-like tumors represents three fundamentally different tumor types. Urobasal tumors maintain an apparent urothelial differentiation axis composed of PPARG/RXRA, FOXA1/GATA3 and anterior HOXA and HOXB genes. Genomically Unstable and SCC-like tumors differ from Urobasal tumors by a strong increase of proliferative activity through the PLK1-FOXM1 axis operating in both subtypes. However, whereas SCC-like tumors evade urothelial differentiation by a block in differentiation through strong downregulation of PPARG/RXRA, FOXA1/GATA3, our data indicates that Genomically Unstable tumors evade differentiation in a more dynamic manner.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 67 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Sweden 1 1%
Denmark 1 1%
Unknown 65 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 20 30%
Student > Ph. D. Student 15 22%
Student > Master 9 13%
Student > Postgraduate 7 10%
Student > Bachelor 4 6%
Other 6 9%
Unknown 6 9%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 23 34%
Agricultural and Biological Sciences 15 22%
Medicine and Dentistry 12 18%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Immunology and Microbiology 2 3%
Other 2 3%
Unknown 11 16%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 January 2016.
All research outputs
#18,411,569
of 22,807,037 outputs
Outputs from BMC Medical Genomics
#862
of 1,223 outputs
Outputs of similar age
#192,626
of 266,750 outputs
Outputs of similar age from BMC Medical Genomics
#25
of 28 outputs
Altmetric has tracked 22,807,037 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,223 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 18th percentile – i.e., 18% of its peers scored the same or lower than it.
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We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one is in the 10th percentile – i.e., 10% of its contemporaries scored the same or lower than it.