Evidence map›Paper›PMID 28249598›Full record

ArticleBMC cancer2017

The prognostic utility of the transcription factor SRF in docetaxel-resistant prostate cancer: in-vitro discovery and in-vivo validation.

D J Lundon, A Boland, M Prencipe, G Hurley, A O'Neill, E Kay, S T Aherne, P Doolan, S F Madden, M Clynes and 3 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

10 citing papers in PubMed, 16 citations in OpenAlex.

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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 4 institutions in 2 countries.

D J LundonUCD School of Medicine, Conway Institute of Biomedical and Biomolecular Sciences, University College Dublin, Belfield, Dublin, Dublin 4, Ireland. Dara.Lundon@ucdconnect.ie.
A BolandUCD School of Mathematical Sciences and Insight, University College Dublin, Belfield, Dublin, Dublin 4, Ireland.
M PrencipeUCD School of Medicine, Conway Institute of Biomedical and Biomolecular Sciences, University College Dublin, Belfield, Dublin, Dublin 4, Ireland.
G HurleyUCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Dublin 4, Ireland.
A O'NeillUCD School of Medicine, Conway Institute of Biomedical and Biomolecular Sciences, University College Dublin, Belfield, Dublin, Dublin 4, Ireland.
E KayDepartment of Pathology, Beaumont Hospital & Royal College of Surgeons in Ireland, Dublin, Ireland.
S T AherneNational Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland Non-US/Non-Canadian, Ireland.
P DoolanNational Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland Non-US/Non-Canadian, Ireland.
S F MaddenUCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Dublin 4, Ireland.
M ClynesNational Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland Non-US/Non-Canadian, Ireland.
C MorrisseyDepartment of Urology, University of Washington, Seattle, WA, USA.
J M FitzpatrickUCD School of Medicine, Conway Institute of Biomedical and Biomolecular Sciences, University College Dublin, Belfield, Dublin, Dublin 4, Ireland.
R W WatsonUCD School of Medicine, Conway Institute of Biomedical and Biomolecular Sciences, University College Dublin, Belfield, Dublin, Dublin 4, Ireland.
University College Dublin · IEDublin City University · IEBeaumont Hospital · IEUniversity of Washington · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDocetaxel based therapy is one of the first line chemotherapeutic agents for the treatment of metastatic castrate-resistant prostate cancer. However, one of the major obstacles in the treatment of these patients is docetaxel-resistance. Defining the mechanisms of resistance so as to inform subsequent treatment options and combinations represents a challenge for clinicians and scientists. Previous work by our group has shown complex changes in pro and anti-apoptotic proteins in the development of resistance to docetaxel. Targeting these changes individually does not significantly impact on the resistant phenotype but understanding the central signalling pathways and transcription factors (TFs) which control these could represent a more appropriate therapeutic targeting approach.

methodsUsing a number of docetaxel-resistant sublines of PC-3 cells, we have undertaken a transcriptomic analysis by expression microarray using the Affymetrix Human Gene 1.0 ST Array and in conjunction with bioinformatic analyses undertook to predict dysregulated TFs in docetaxel resistant prostate cancer. The clinical significance of this prediction was ascertained by performing immunohistochemical (IHC) analysis of an identified TF (SRF) in the metastatic sites from men who died of advanced CRPC. Investigation of the functional role of SRF was examined by manipulating SRF using SiRNA in a docetaxel-resistant PC-3 cell line model.

resultsThe transcription factors identified include serum response factor (SRF), nuclear factor kappa-B (NFκB), heat shock factor protein 1 (HSF1), testicular receptor 2 & 4 (TR2 &4), vitamin-D and retinoid x receptor (VDR-RXR) and oestrogen-receptor 1 (ESR1), which are predicted to be responsible for the differential gene expression observed in docetaxel-resistance. IHC analysis to quantify nuclear expression of the identified TF SRF correlates with both survival from date of bone metastasis (p = 0.003), survival from androgen independence (p = 0.00002), and overall survival from prostate cancer (p = 0.0044). Functional knockdown of SRF by siRNA demonstrated a reversal of apoptotic resistance to docetaxel treatment in the docetaxel-resistant PC-3 cell line model.

conclusionsOur results suggest that SRF could aid in treatment stratification of prostate cancer, and may also represent a therapeutic target in the treatment of men afflicted with advanced prostate cancer.

Indexed as

Drug Resistance, NeoplasmBone NeoplasmsCell Line, TumorDocetaxelGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleOligonucleotide Array Sequence AnalysisPrognosisProstatic NeoplasmsSerum Response FactorSurvival AnalysisTaxoidsTranscriptional ActivationTranscription FactorsDocetaxelSerum Response FactorSRF protein, humanTaxoidsTranscription FactorsAdenocarcinoma of prostateAndrogen-independent prostatic cancerAnti-neoplastic agent resistanceDocetaxel resistanceDrug resistanceMetastatic prostate cancerPersonalised medicineProstate CancerTranslational oncology

Identifiers

PMID28249598
PMCPMC5333466
OpenAlexW2593417901

What OpenQuestion holds

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LicenceCC BY
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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.