Evidence map›Paper›PMID 27166397›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016

Analytic Validation of RNA In Situ Hybridization (RISH) for AR and AR-V7 Expression in Human Prostate Cancer.

Liana B Guedes, Carlos L Morais, Fawaz Almutairi, Michael C Haffner, Qizhi Zheng, John T Isaacs, Emmanuel S Antonarakis, Changxue Lu, Harrison Tsai, Jun Luo and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 4% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Pooled it
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  15. MSH2 Loss in Primary Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
    Article
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  18. Androgen Receptor Variant AR-V9 Is Coexpressed with AR-V7 in Prostate Cancer Metastases and Predicts Abiraterone Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
    Observational
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Liana B GuedesDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Carlos L MoraisDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Fawaz AlmutairiDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Michael C HaffnerDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Qizhi ZhengDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
John T IsaacsDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Emmanuel S AntonarakisDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Changxue LuDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Harrison TsaiDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Jun LuoDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Angelo M De MarzoDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Tamara L LotanDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. tlotan1@jhmi.edu.
Johns Hopkins University · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
TRANSGENIC MODELS FOR PROSTATE CANCER AND AUTOIMMUNITYP50CA058236 · NCI · JOHNS HOPKINS UNIVERSITY · PI DENMEADE, SAMUEL R · 1992 to 2020
$43.9M
The aberrant androgen receptor underlies abiraterone/enzalutamide resistanceR01CA185297 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANTONARAKIS, EMMANUEL S., LUO, JUN · 2015 to 2018
$1.5M
NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA058236NCI NIH HHS R01 CA185297
6 · The paper itself

Abstract

purposeRNA expression of androgen receptor splice variants may be a biomarker of resistance to novel androgen deprivation therapies in castrate-resistant prostate cancer (CRPC). We analytically validated an RNA in situ hybridization (RISH) assay for total AR and AR-V7 for use in formalin-fixed paraffin-embedded (FFPE) prostate tumors. EXPERIMENTAL

designWe used prostate cell lines and xenografts to validate chromogenic RISH to detect RNA containing AR exon 1 (AR-E1, surrogate for total AR RNA species) and cryptic exon 3 (AR-CE3, surrogate for AR-V7 expression). RISH signals were quantified in FFPE primary tumors and CRPC specimens, comparing to known AR and AR-V7 status by IHC and RT-PCR.

resultsThe quantified RISH results correlated significantly with total AR and AR-V7 levels by RT-PCR in cell lines, xenografts, and autopsy metastases. Both AR-E1 and AR-CE3 RISH signals were localized in nuclear punctae in addition to the expected cytoplasmic speckles. Compared with admixed benign glands, AR-E1 expression was significantly higher in primary tumor cells with a median fold increase of 3.0 and 1.4 in two independent cohorts (P < 0.0001 and P = 0.04, respectively). While AR-CE3 expression was detectable in primary prostatic tumors, levels were substantially higher in a subset of CRPC metastases and cell lines, and were correlated with AR-E1 expression.

conclusionsRISH for AR-E1 and AR-CE3 is an analytically valid method to examine total AR and AR-V7 RNA levels in FFPE tissues. Future clinical validation studies are required to determine whether AR RISH is a prognostic or predictive biomarker in specific clinical contexts. Clin Cancer Res; 22(18); 4651-63. ©2016 AACR.

Indexed as

In Situ HybridizationRNA IsoformsAnimalsBiomarkers, TumorComputational BiologyDisease Models, AnimalGene ExpressionHeterograftsHumansImage-Guided BiopsyMaleMiceNeoplasm GradingNeoplasm MetastasisProstatic NeoplasmsReceptors, AndrogenBiomarkers, TumorReceptors, AndrogenRNA Isoforms

Identifiers

PMID27166397
PMCPMC5026571
OpenAlexW2355865626

What OpenQuestion holds

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Registered trials

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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.