Evidence map›Paper›PMID 23840389›Full record

ArticlePloS one2013

RNA-Seq Differentiates Tumour and Host mRNA Expression Changes Induced by Treatment of Human Tumour Xenografts with the VEGFR Tyrosine Kinase Inhibitor Cediranib.

James R Bradford, Matthew Farren, Steve J Powell, Sarah Runswick, Susie L Weston, Helen Brown, Oona Delpuech, Mark Wappett, Neil R Smith, T Hedley Carr and 3 more

Open access · goldAbstract readComparative Study
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

21 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
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  3. RNA-Seq Data Processing in Plant-Pathogen Interaction System: A Case Study.Methods in molecular biology (Clifton, N.J.) · 2023
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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

13 authors at 2 institutions in 2 countries.

James R BradfordOncology, AstraZeneca Pharmaceuticals, Alderley Park, Cheshire, United Kingdom.
Matthew Farren
Steve J Powell
Sarah Runswick
Susie L Weston
Helen Brown
Oona Delpuech
Mark Wappett
Neil R Smith
T Hedley Carr
Jonathan R Dry
Neil J Gibson
Simon T Barry
AstraZeneca (United Kingdom) · GBAstraZeneca (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pre-clinical models of tumour biology often rely on propagating human tumour cells in a mouse. In order to gain insight into the alignment of these models to human disease segments or investigate the effects of different therapeutics, approaches such as PCR or array based expression profiling are often employed despite suffering from biased transcript coverage, and a requirement for specialist experimental protocols to separate tumour and host signals. Here, we describe a computational strategy to profile transcript expression in both the tumour and host compartments of pre-clinical xenograft models from the same RNA sample using RNA-Seq. Key to this strategy is a species-specific mapping approach that removes the need for manipulation of the RNA population, customised sequencing protocols, or prior knowledge of the species component ratio. The method demonstrates comparable performance to species-specific RT-qPCR and a standard microarray platform, and allowed us to quantify gene expression changes in both the tumour and host tissue following treatment with cediranib, a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor, including the reduction of multiple murine transcripts associated with endothelium or vessels, and an increase in genes associated with the inflammatory response in response to cediranib. In the human compartment, we observed a robust induction of hypoxia genes and a reduction in cell cycle associated transcripts. In conclusion, the study establishes that RNA-Seq can be applied to pre-clinical models to gain deeper understanding of model characteristics and compound mechanism of action, and to identify both tumour and host biomarkers.

Indexed as

AnimalsCarcinoma, Non-Small-Cell LungCell CycleCell HypoxiaCell Line, TumorComputational BiologyGene Expression ProfilingGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansIndolesLung NeoplasmsMiceOligonucleotide Array Sequence AnalysisProtein Kinase InhibitorsQuinazolinescediranibIndolesProtein Kinase InhibitorsQuinazolines

Identifiers

PMID23840389
PMCPMC3686868
OpenAlexW2071439868

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.