Evidence map›Paper›PMID 31104332›Full record

ArticleThe Prostate2019

Increased EZH2 expression in prostate cancer is associated with metastatic recurrence following external beam radiotherapy.

Xiaoning Wu, Helen Scott, Sigrid V Carlsson, Daniel D Sjoberg, Lucia Cerundolo, Hans Lilja, Remko Prevo, Guillaume Rieunier, Valentine Macaulay, Geoffrey S Higgins and 6 more

Open access · hybridAbstract read
In one paragraph

Article in The Prostate, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

24 citing papers in PubMed, 35 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

16 authors at 4 institutions in 3 countries.

Xiaoning WuDepartment of Oncology, CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.
Helen ScottDepartment of Oncology, CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.
Sigrid V CarlssonDepartment of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Daniel D SjobergDepartment of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Lucia CerundoloNuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
Hans LiljaNuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
Remko PrevoDepartment of Oncology, CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.
Guillaume RieunierDepartment of Oncology, University of Oxford, Oxford, United Kingdom.
Valentine MacaulayDepartment of Oncology, University of Oxford, Oxford, United Kingdom.
Geoffrey S HigginsDepartment of Oncology, CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.
Clare L VerrillNuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
Alastair D LambNuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
Vincent T CunliffeDepartment of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
Chas BountraNuffield Department of Medicine, Structural Genomics Consortium, University of Oxford, Oxford, United Kingdom.
Freddie C HamdyNuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
Richard J BryantDepartment of Oncology, CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-8330-9251
Nuffield Orthopaedic Centre · GBUniversity of Oxford · GBMemorial Sloan Kettering Cancer Center · USUniversity of Sheffield · GB

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
SPORE In Prostate CancerP50CA092629 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI JAMES A EASTHAM · 2001 to 2026
$63.0M
Breast Cancer Now 6525Cancer Research UK 19590Cancer Research UK 22748Cancer Research UK 25812Cancer Research UK C39297/A22748Department of HealthMedical Research CouncilNCI NIH HHS P30 CA008748NCI NIH HHS P50 CA092629NIH HHS P30 CA008748NIH HHS P50 CA092629
6 · The paper itself

Abstract

backgroundEnhancer of zeste 2 (EZH2) promotes prostate cancer progression. We hypothesized that increased EZH2 expression is associated with postradiotherapy metastatic disease recurrence, and may promote radioresistance.

methodsEZH2 expression was investigated using immunohistochemistry in diagnostic prostate biopsies of 113 prostate cancer patients treated with radiotherapy with curative intent. Associations between EZH2 expression in malignant and benign tissue in prostate biopsy cores and outcomes were investigated using univariate and multivariate Cox regression analyses. LNCaP and PC3 cell radiosensitivity was investigated using colony formation and γH2AX assays following UNC1999 chemical probe-mediated EZH2 inhibition.

resultsWhile there was no significant association between EZH2 expression and biochemical recurrence following radiotherapy, univariate analysis revealed that prostate cancer cytoplasmic and total EZH2 expression were significantly associated with metastasis development postradiotherapy (P = 0.034 and P = 0.003, respectively). On multivariate analysis, the prostate cancer total EZH2 expression score remained statistically significant (P = 0.003), while cytoplasmic EZH2 expression did not reach statistical significance (P = 0.053). No association was observed between normal adjacent prostate EZH2 expression and biochemical recurrence or metastasis. LNCaP and PC3 cell treatment with UNC1999 reduced histone H3 lysine 27 tri-methylation levels. Irradiation of LNCaP or PC3 cells with a single 2 Gy fraction with UNC1999-mediated EZH2 inhibition resulted in a statistically significant, though modest, reduction in cell colony number for both cell lines. Increased γH2AX foci were observed 24 hours after ionizing irradiation in LNCaP cells, but not in PC3, following UNC1999-mediated EZH2 inhibition vs controls.

conclusionsTaken together, these results reveal that high pretreatment EZH2 expression in prostate cancer in diagnostic biopsies is associated with an increased risk of postradiotherapy metastatic disease recurrence, but EZH2 function may only at most play a modest role in promoting prostate cancer cell radioresistance.

Indexed as

Bone NeoplasmsCell Line, TumorDisease ProgressionEnhancer of Zeste Homolog 2 ProteinHumansMaleNeoplasm GradingProstateProstatic NeoplasmsSoft Tissue NeoplasmsEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanenhancer of zeste 2prostate cancerradiotherapy

Identifiers

PMID31104332
PMCPMC6563086
OpenAlexW2946589687

What OpenQuestion holds

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LicenceCC BY
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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.