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Comprehensive Profiling of the Androgen Receptor in Liquid Biopsies from Castration-resistant Prostate Cancer Reveals Novel Intra-AR Structural Variation and Splice Variant Expression Patterns

Overview of attention for article published in European Urology, August 2017
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (90th percentile)
  • Good Attention Score compared to outputs of the same age and source (76th percentile)

Mentioned by

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26 tweeters
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3 patents
facebook
3 Facebook pages

Citations

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59 Dimensions

Readers on

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97 Mendeley
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Title
Comprehensive Profiling of the Androgen Receptor in Liquid Biopsies from Castration-resistant Prostate Cancer Reveals Novel Intra-AR Structural Variation and Splice Variant Expression Patterns
Published in
European Urology, August 2017
DOI 10.1016/j.eururo.2017.01.011
Pubmed ID
Authors

Bram De Laere, Pieter-Jan van Dam, Tom Whitington, Markus Mayrhofer, Emanuela Henao Diaz, Gert Van den Eynden, Jean Vandebroek, Jurgen Del-Favero, Steven Van Laere, Luc Dirix, Henrik Grönberg, Johan Lindberg

Abstract

Expression of the androgen receptor splice variant 7 (AR-V7) is associated with poor response to second-line endocrine therapy in castration-resistant prostate cancer (CRPC). However, a large fraction of nonresponding patients are AR-V7-negative. To investigate if a comprehensive liquid biopsy-based AR profile may improve patient stratification in the context of second-line endocrine therapy. Peripheral blood was collected from patients with CRPC (n=30) before initiation of a new line of systemic therapy. We performed profiling of circulating tumour DNA via low-pass whole-genome sequencing and targeted sequencing of the entire AR gene, including introns. Targeted RNA sequencing was performed on enriched circulating tumour cell fractions to assess the expression levels of seven AR splice variants (ARVs). Somatic AR variations, including copy-number alterations, structural variations, and point mutations, were combined with ARV expression patterns and correlated to clinicopathologic parameters. Collectively, any AR perturbation, including ARV, was detected in 25/30 patients. Surprisingly, intra-AR structural variation was present in 15/30 patients, of whom 14 expressed ARVs. The majority of ARV-positive patients expressed multiple ARVs, with AR-V3 the most abundantly expressed. The presence of any ARV was associated with progression-free survival after second-line endocrine treatment (hazard ratio 4.53, 95% confidence interval 1.424-14.41; p=0.0105). Six out of 17 poor responders were AR-V7-negative, but four carried other AR perturbations. Comprehensive AR profiling, which is feasible using liquid biopsies, is necessary to increase our understanding of the mechanisms underpinning resistance to endocrine treatment. Alterations in the androgen receptor are associated with endocrine treatment outcomes. This study demonstrates that it is possible to identify different types of alterations via simple blood draws. Follow-up studies are needed to determine the effect of such alterations on hormonal therapy.

Twitter Demographics

The data shown below were collected from the profiles of 26 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 97 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Belgium 2 2%
Unknown 95 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 25 26%
Researcher 20 21%
Student > Bachelor 10 10%
Student > Master 10 10%
Student > Doctoral Student 6 6%
Other 16 16%
Unknown 10 10%
Readers by discipline Count As %
Medicine and Dentistry 25 26%
Biochemistry, Genetics and Molecular Biology 22 23%
Agricultural and Biological Sciences 18 19%
Pharmacology, Toxicology and Pharmaceutical Science 7 7%
Computer Science 2 2%
Other 6 6%
Unknown 17 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 20. 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 19 November 2019.
All research outputs
#1,084,196
of 16,227,909 outputs
Outputs from European Urology
#881
of 4,805 outputs
Outputs of similar age
#32,883
of 358,137 outputs
Outputs of similar age from European Urology
#35
of 151 outputs
Altmetric has tracked 16,227,909 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,805 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one has done well, scoring higher than 81% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 358,137 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 90% of its contemporaries.
We're also able to compare this research output to 151 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.