Evidence map›Paper›PMID 27577081›Full record

ArticleOncotarget2016

DNA methylation array analysis identifies breast cancer associated RPTOR, MGRN1 and RAPSN hypomethylation in peripheral blood DNA.

Qiuqiong Tang, Tim Holland-Letz, Alla Slynko, Katarina Cuk, Frederik Marme, Sarah Schott, Jörg Heil, Bin Qu, Michael Golatta, Melanie Bewerunge-Hudler and 11 more

Open access · diamondAbstract readComparative StudyValidation Study
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 3 pooled it
3.0field-weighted citation impact, top 9% 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, 3 syntheses or guidelines pooled it, 38 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
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    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 6 institutions in 1 country.

Qiuqiong TangMolecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
Tim Holland-LetzDivision of Biostatistics (C060), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Alla SlynkoDivision of Biostatistics (C060), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Katarina CukMolecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
Frederik MarmeMolecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
Sarah SchottMolecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
Jörg HeilDepartment of Gynecology and Obstetrics, University Women's Clinic, Heidelberg, Germany.
Bin QuDepartment of Biophysics, Center for Integrated Physiology and Molecular Medicine (CIPMM), Saarland University, Homburg (Saar), Germany.
Michael GolattaDepartment of Gynecology and Obstetrics, University Women's Clinic, Heidelberg, Germany.
Melanie Bewerunge-HudlerGenomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Christian SutterInstitute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
Harald SurowyMolecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
Barbara WappenschmidtCentre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, Cologne, Germany.
Rita SchmutzlerCentre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, Cologne, Germany.
Markus HothDepartment of Biophysics, Center for Integrated Physiology and Molecular Medicine (CIPMM), Saarland University, Homburg (Saar), Germany.
Peter BugertInstitute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, German Red Cross Blood Service Baden, Württemberg, Hessen, Mannheim, Germany.
Claus R BartramInstitute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
Christof SohnMolecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
Andreas SchneeweissMolecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
Rongxi YangMolecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
Barbara BurwinkelMolecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
Heidelberg University · DEGerman Cancer Research Center · DESaarland University · DEUniversity Hospital Cologne · DEUniversity Hospital Heidelberg · DENational Center for Tumor Diseases · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA methylation changes in peripheral blood DNA have been shown to be associated with solid tumors. We sought to identify methylation alterations in whole blood DNA that are associated with breast cancer (BC). Epigenome-wide DNA methylation profiling on blood DNA from BC cases and healthy controls was performed by applying Infinium HumanMethylation450K BeadChips. Promising CpG sites were selected and validated in three independent larger sample cohorts via MassARRAY EpiTyper assays. CpG sites located in three genes (cg06418238 in RPTOR, cg00736299 in MGRN1 and cg27466532 in RAPSN), which showed significant hypomethylation in BC patients compared to healthy controls in the discovery cohort (p < 1.00 x 10-6) were selected and successfully validated in three independent cohorts (validation I, n =211; validation II, n=378; validation III, n=520). The observed methylation differences are likely not cell-type specific, as the differences were only seen in whole blood, but not in specific sub cell-types of leucocytes. Moreover, we observed in quartile analysis that women in the lower methylation quartiles of these three loci had higher ORs than women in the higher quartiles. The combined AUC of three loci was 0.79 (95%CI 0.73-0.85) in validation cohort I, and was 0.60 (95%CI 0.54-0.66) and 0.62 (95%CI 0.57-0.67) in validation cohort II and III, respectively. Our study suggests that hypomethylation of CpG sites in RPTOR, MGRN1 and RAPSN in blood is associated with BC and might serve as blood-based marker supplements for BC if these could be verified in prospective studies.

Indexed as

DNA MethylationEpigenesis, GeneticOligonucleotide Array Sequence AnalysisAdultAgedArea Under CurveBiomarkers, TumorBreast NeoplasmsCirculating Tumor DNACpG IslandsFemaleGene Expression ProfilingGenetic Predisposition to DiseaseHumansLogistic ModelsMiddle AgedBiomarkers, TumorCirculating Tumor DNAMGRN1 protein, humanMuscle Proteinsperipheral membrane protein 43KRegulatory-Associated Protein of mTORRPTOR protein, humanUbiquitin-Protein Ligasesbreast cancerDNA methylationMGRN1RAPSNRPTOR

Identifiers

PMID27577081
PMCPMC5325435
OpenAlexW2507799542

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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.