Evidence map›Paper›PMID 23108258›Full record

ArticleEpigenetics2012

Epigenetic biomarkers of T-cells in human glioma.

John K Wiencke, William P Accomando, Shichun Zheng, Joe Patoka, Xiaoqin Dou, Joanna J Phillips, George Hsuang, Brock C Christensen, E Andres Houseman, Devin C Koestler and 5 more

Abstract read
In one paragraph

Article in Epigenetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

26 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  18. Molecular signatures of major depression.Current biology : CB · 2015
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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

15 authors.

John K WienckeDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA USA. John.Wiencke@ucsf.edu
William P Accomando
Shichun Zheng
Joe Patoka
Xiaoqin Dou
Joanna J Phillips
George Hsuang
Brock C Christensen
E Andres Houseman
Devin C Koestler
Paige Bracci
Joseph L Wiemels
Margaret Wrensch
Heather H Nelson
Karl T Kelsey

Funding

Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
WILD TYPE P53-BASED ADJUVANT IMMUNOTHERAPY FOR SCCHNP50CA097190 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 2004 to 2026
$49.6M
GENETIC EPIDEMIOLOGY OF MALIGNANT GLIOMAR01CA052689 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WIENCKE, JOHN K., WRENSCH, MARGARET R. · 1991 to 2015
$20.5M
BIOMARKERS OF LUNG CANCER SUSCEPTIBILITY IN MINORITIESR01ES006717 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WIENCKE, JOHN K. · 1994 to 2009
$8.9M
Patterns of Somatic Gene Alterations in Oral CancerR01CA100679 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI KELSEY, KARL TIMOTHY · 2004 to 2012
$2.6M
The Epidemiology of Molecular Alterations in MesotheliomaR01CA126939 · NCI · BROWN UNIVERSITY · PI KELSEY, KARL TIMOTHY · 2008 to 2012
$2.4M
The role of microglia and macrophages in the development of brain tumorsK08NS063456 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PHILLIPS, JOANNA · 2008 to 2012
$854k
NCI NIH HHS CA100679NCI NIH HHS CA126939NCI NIH HHS P50 CA097190NCI NIH HHS P50 CA097257NCI NIH HHS P50CA097257NCI NIH HHS R01 CA052689NCI NIH HHS R01 CA100679NCI NIH HHS R01CA52689NIEHS NIH HHS ES06717NIEHS NIH HHS R01 ES006717NINDS NIH HHS K08 NS063456
6 · The paper itself

Abstract

Immune factors are thought to influence glioma risk and outcomes, but immune profiling studies to further our understanding of the immune response are limited by current immunodiagnostic methods. We developed a new assay to capture glioma immune biology based on quantitative methylation specific PCR (qMSP) of two T-cell genes (CD3Z: T-cells, and FOXP3: Tregs). Flow cytometry of T-cells correlated well with the CD3Z demethylation assay (r = 0.93; p < 2.2 × 10 (-16) ), demonstrating the validity of the assay. Furthermore, there was a high correlation between qMSP and immunohistochemistry (IHC) in quantifying tumor infiltrating T-cells (r = 0.85; p = 3.4 × 10 (-11) ). Applying our qMSP methods to archival whole blood from 65 glioblastoma multiforme (GBM) cases and 94 non-diseased controls, GBM cases had highly statistically significantly lower T-cells (p = 1.7 × 10 (-9) ) as well as Tregs (p = 5.2 × 10 (-11) ) and a modestly lower ratio of Tregs/T-cells (p = 0.024). Applying the methods to 120 excised glioma tumors, we observed that tumor infiltrating CD3+ T-cells were positively correlated with glioma tumor grade (p = 5.7 × 10 (-7) ), and that Tregs were enriched in tumors compared with peripheral blood indicating active chemoattraction of suppressive Tregs into the tumor compartment. Poorer patient survival was correlated with higher levels of tumor infiltrating T-cells (p = 0.01) and Tregs (p = 0.04). DNA methylation based immunodiagnostics represent a new generation of powerful laboratory tools offering many advantages over conventional methods that will facilitate large clinical epidemiologic studies and capitalize on stored archival blood and tissue banks.

Indexed as

DNA MethylationEpigenesis, GeneticAdultAgedAged, 80 and overBiomarkers, TumorBrain NeoplasmsCase-Control StudiesCD3 ComplexFemaleFlow CytometryForkhead Transcription FactorsGlioblastomaGliomaHumansLymphocytes, Tumor-InfiltratingBiomarkers, TumorCD3 antigen, zeta chainCD3 ComplexForkhead Transcription FactorsFOXP3 protein, human

Identifiers

PMID23108258
PMCPMC3528694

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.