Evidence map›Paper›PMID 31902687›Full record

ArticleGynecologic oncology2020

Analysis of DNA methylation in endometrial biopsies to predict risk of endometrial cancer.

Francesco Multinu, Jun Chen, Joseph D Madison, Michelle Torres, Jvan Casarin, Daniel Visscher, Viji Shridhar, Jamie Bakkum-Gamez, Mark Sherman, Nicolas Wentzensen and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Gynecologic oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 10% 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

20 citing papers in PubMed, 28 citations in OpenAlex.

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  16. HypermethylatedFrontiers in oncology · 2022
    Article
  17. Frontiers in microbiology · 2021
    Article
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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

12 authors at 4 institutions in 1 country.

Francesco MultinuDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, United States of America.
Jun ChenDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, United States of America.
Joseph D MadisonDepartment of Surgery, Mayo Clinic, Rochester, MN, United States of America; Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, United States of America.
Michelle TorresDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, United States of America.
Jvan CasarinDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, United States of America.
Daniel VisscherDepartment of Laboratory Medicine, Mayo Clinic, Rochester, MN, United States of America.
Viji ShridharDepartment of Laboratory Medicine, Mayo Clinic, Rochester, MN, United States of America.
Jamie Bakkum-GamezDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, United States of America.
Mark ShermanDepartment of Health Sciences Research and Division of Epidemiology, Mayo Clinic, Jacksonville, FL, United States of America.
Nicolas WentzensenDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States of America.
Andrea MarianiDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, United States of America.
Marina Walther-AntonioDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, United States of America; Department of Surgery, Mayo Clinic, Rochester, MN, United States of America; Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, United States of America. Electronic address: WaltherAntonio.Marina@mayo.edu.
Mayo Clinic · USMayo Clinic in Florida · USWinnMed · USDivision of Cancer Epidemiology and Genetics

Funding

Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI ELLEN L. GOODE · 2009 to 2026
$37.0M
ZESTRIL VS. VERAPAMIL IN THE TREATMENT OF HYPERTENSIONM01RR000585 · NCRR · MAYO CLINIC ROCHESTER · PI RIZZA, ROBERT A. · 1985 to 2006
$30.4M
Institutional Career Development CoreKL2TR002379 · NCATS · MAYO CLINIC ROCHESTER · PI NILUFER ERTEKIN-TANER · 2017 to 2026
$14.9M
NCATS NIH HHS KL2 TR002379NCI NIH HHS P50 CA136393NCRR NIH HHS M01 RR000585
6 · The paper itself

Abstract

objectiveTo determine whether analysis of methylated DNA in benign endometrial biopsy (EB) specimens is associated with risk of endometrial cancer (EC).

methodsWe identified 23 women with EBs performed at Mayo Clinic diagnosed as normal (n = 14) or hyperplasia (n = 9) and who later developed endometrial cancer after a median interval of 1 year. Cases were matched 1:1 with patients with benign EBs who did not develop EC (controls) by histology of benign EB (normal endometrium vs. endometrial hyperplasia without atypia), date of EB, age at EB, and length of post-biopsy follow-up. DNA extracted from formalin-fixed paraffin-embedded tissues underwent pyrosequencing to determine percent methylation of promoter region CpGs at 26 loci in 4 genes (ADCYAP1, HAND2, MME, RASSF1A) previously reported as methylated in EC.

resultsAfter pathologic review, 23 matched pairs of cases and controls were identified (14 normal, 9 hyperplasia without atypia per group). Among cases, median time from benign EB to EC was 1 year (range 2 days - 9.2 years). We evaluated 26 CpG sites within 4 genes and found a consistent trend of increasing percentage of methylation from control to case to EC for all CpGs. At the gene-level, mean methylation events of ADCYAP1 and HAND2 in cases were significantly higher than control (p = 0.015 and p = 0.021, respectively). Though the other genes did not reach statistical significance, we observed an increased methylation trend among all genes. Area-under-curve (AUC) calculations (predicting future development of EC in the setting of benign EB) for ADCYAP1 and HAND2 were 0.71 (95% CI 0.55-0.88) and 0.83 (95% CI 0.64-1, respectively).

conclusionsThis proof-of-principle study provides evidence that specific methylation patterns in benign EB correlate with future development of EC.

Indexed as

DNA MethylationAdultBiopsyCase-Control StudiesDNADNA, NeoplasmEndometrial NeoplasmsEndometriumFemaleGenetic Predisposition to DiseaseHumansMiddle AgedDNADNA, Neoplasm

Identifiers

PMID31902687
PMCPMC7056503
OpenAlexW2998116497

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.