Evidence map›Paper›PMID 28866255›Full record

ArticleEuropean urology2018

Novel Junction-specific and Quantifiable In Situ Detection of AR-V7 and its Clinical Correlates in Metastatic Castration-resistant Prostate Cancer.

Yezi Zhu, Adam Sharp, Courtney M Anderson, John L Silberstein, Maritza Taylor, Changxue Lu, Pei Zhao, Angelo M De Marzo, Emmanuel S Antonarakis, Mindy Wang and 14 more

Open access · greenAbstract readComparative StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in European urology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 5 pooled it
7.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 5 syntheses or guidelines pooled it, 59 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Use of Automated BaseScope Assay on the Leica BOND RX.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Assessment of Androgen Receptor Splice Variant-7 as a Biomarker of Clinical Response in Castration-Sensitive Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 6 institutions in 2 countries.

Yezi ZhuDepartment of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Adam SharpThe Institute for Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK.
Courtney M AndersonAdvanced Cell Diagnostics, Newark, CA, USA.
John L SilbersteinDepartment of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Maritza TaylorDepartment of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Changxue LuDepartment of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Pei ZhaoDepartment of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Angelo M De MarzoDepartment of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Emmanuel S AntonarakisDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mindy WangAdvanced Cell Diagnostics, Newark, CA, USA.
Xingyong WuAdvanced Cell Diagnostics, Newark, CA, USA.
Yuling LuoAdvanced Cell Diagnostics, Newark, CA, USA.
Nan SuAdvanced Cell Diagnostics, Newark, CA, USA.
Daniel Nava RodriguesThe Institute for Cancer Research, London, UK.
Ines FigueiredoThe Institute for Cancer Research, London, UK.
Jonathan WeltiThe Institute for Cancer Research, London, UK.
Emily ParkAdvanced Cell Diagnostics, Newark, CA, USA.
Xiao-Jun MaAdvanced Cell Diagnostics, Newark, CA, USA.
Ilsa ColemanFred Hutchinson Cancer Research Center, Seattle, WA, USA.
Colm MorrisseyUniversity of Washington, Seattle, WA, USA.
Stephen R PlymateUniversity of Washington, Seattle, WA, USA.
Peter S NelsonFred Hutchinson Cancer Research Center, Seattle, WA, USA; University of Washington, Seattle, WA, USA.
Johann S de BonoThe Institute for Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK. Electronic address: johann.de-bono@icr.ac.uk.
Jun LuoDepartment of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jluo1@jhmi.edu.
Advanced Cell Diagnostics (United States) · USJohns Hopkins Medicine · USJohns Hopkins University · USUniversity of Washington · USRoyal Marsden NHS Foundation Trust · GBFred Hutch Cancer Center · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
TRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETER S NELSON · 2002 to 2026
$58.1M
TRANSGENIC MODELS FOR PROSTATE CANCER AND AUTOIMMUNITYP50CA058236 · NCI · JOHNS HOPKINS UNIVERSITY · PI DENMEADE, SAMUEL R · 1992 to 2020
$43.9M
Steroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Steven P. Balk · 2013 to 2026
$25.0M
The aberrant androgen receptor underlies abiraterone/enzalutamide resistanceR01CA185297 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANTONARAKIS, EMMANUEL S., LUO, JUN · 2015 to 2018
$1.5M
Targeting the Metabolome in Androgen Receptor-driven Castration-resistant Prostate CancerI01BX003324 · VA · VA PUGET SOUND HEALTHCARE SYSTEM · PI PLYMATE, STEPHEN R. · 2016 to 2024
–
BLRD VA I01 BX003324Cancer Research UKDepartment of HealthMedical Research Council MR/M018318/1NCI NIH HHS P01 CA163227NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA058236NCI NIH HHS P50 CA097186NCI NIH HHS R01 CA185297
6 · The paper itself

Abstract

backgroundAndrogen receptor splice variant 7 (AR-V7) has been implicated in resistance to abiraterone and enzalutamide treatment in men with metastatic castration-resistant prostate cancer (mCRPC). Tissue- or cell-based in situ detection of AR-V7, however, has been limited by lack of specificity.

objectiveTo address current limitations in precision measurement of AR-V7 by developing a novel junction-specific AR-V7 RNA in situ hybridization (RISH) assay compatible with automated quantification. DESIGN, SETTING, AND

participantsWe designed a RISH method to visualize single splice junctions in cells and tissue. Using the validated assay for junction-specific detection of the full-length AR (AR-FL) and AR-V7, we generated quantitative data, blinded to clinical data, for 63 prostate tumor biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated clinical correlates of AR-FL/AR-V7 measurements, including association with prostate-specific antigen progression-free survival (PSA-PFS) and clinical and radiographic progression-free survival (PFS), in a subset of patients starting treatment with abiraterone or enzalutamide following biopsy. RESULTS AND LIMITATIONS: Quantitative AR-FL/AR-V7 data were generated from 56 of the 63 (88.9%) biopsy specimens examined, of which 44 were mCRPC biopsies. Positive AR-V7 signals were detected in 34.1% (15/44) mCRPC specimens, all of which also co-expressed AR-FL. The median AR-V7/AR-FL ratio was 11.9% (range 2.7-30.3%). Positive detection of AR-V7 was correlated with indicators of high disease burden at baseline. Among the 25 CRPC biopsies collected before treatment with abiraterone or enzalutamide, positive AR-V7 detection, but not higher AR-FL, was significantly associated with shorter PSA-PFS (hazard ratio 2.789, 95% confidence interval 1.12-6.95; p=0.0081).

conclusionsWe report for the first time a RISH method for highly specific and quantifiable detection of splice junctions, allowing further characterization of AR-V7 and its clinical significance. PATIENT SUMMARY: Higher AR-V7 levels detected and quantified using a novel method were associated with poorer response to abiraterone or enzalutamide in prostate cancer.

Indexed as

AgedAndrogen AntagonistsBiopsy, NeedleDisease-Free SurvivalHumansImmunohistochemistryIn Situ HybridizationLogistic ModelsMaleMiddle AgedMultivariate AnalysisNeoplasm InvasivenessNeoplasm MetastasisNeoplasm StagingPrognosisProstatic Neoplasms, Castration-ResistantAndrogen AntagonistsProtein IsoformsReceptors, AndrogenAndrogen receptorAR-V7RNA in situ hybridizationSplice variant

Identifiers

PMID28866255
PMCPMC6538073
OpenAlexW2750951140

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.