Evidence map›Paper›PMID 34903270›Full record

ArticleClinical epigenetics2021

High performance methylated DNA markers for detection of colon adenocarcinoma.

Romy A M Klein Kranenbarg, Abdul Hussain Vali, Jan N M IJzermans, Thomas R Pisanic, Tza-Huei Wang, Nilofer Azad, Saraswati Sukumar, Mary Jo Fackler

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 7% 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, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Review
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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

8 authors at 2 institutions in 2 countries.

Romy A M Klein KranenbargDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abdul Hussain ValiDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jan N M IJzermansDepartment of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Thomas R PisanicInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Tza-Huei WangInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Nilofer AzadDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Saraswati SukumarDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. saras@jhmi.edu.ORCID 0000-0002-5656-6703
Mary Jo FacklerDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. facklma@jhmi.edu.ORCID 0000-0002-7249-3807
Johns Hopkins University · USErasmus MC · NL

Funding

Tumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI JAFFEE, ELIZABETH M. · 1993 to 2022
$54.6M
NCI NIH HHS P50 CA062924
6 · The paper itself

Abstract

backgroundColon cancer (CC) is treatable if detected in its early stages. Improved CC detection assays that are highly sensitive, specific, and available at point of care are needed. In this study, we systematically selected and tested methylated markers that demonstrate high sensitivity and specificity for detection of CC in tissue and circulating cell-free DNA.

methodsHierarchical analysis of 22 candidate CpG loci was conducted using The Cancer Genome Atlas (TCGA) COAD 450K HumanMethylation database. Methylation of 13 loci was analyzed using quantitative multiplex methylation-specific PCR (QM-MSP) in a training set of fresh frozen colon tissues (N = 53). Hypermethylated markers were identified that were highest in cancer and lowest in normal colon tissue using the 75th percentile in Mann-Whitney analyses and the receiver operating characteristic (ROC) statistic. The cumulative methylation status of the marker panel was assayed in an independent test set of fresh frozen colon tissues (N = 52) using conditions defined and locked in the training set. A minimal marker panel of 6 genes was defined based on ROC area under the curve (AUC). Plasma samples (N = 20 colorectal cancers, stage IV and N = 20 normal) were tested by cMethDNA assay to evaluate marker performance in liquid biopsy.

resultsIn the test set of samples, compared to normal tissue, a 6-gene panel showed 100% sensitivity and 90% specificity for detection of CC, and an AUC of 1.00 (95% CI 1.00, 1.00). In stage IV colorectal cancer plasma versus normal, an 8-gene panel showed 95% sensitivity, 100% specificity, and an AUC of 0.996 (95% CI 0.986, 1.00) while a 5-gene subset showed 100% sensitivity, 100% specificity, and an AUC of 1.00 (95% CI 1.00, 1.00), highly concordant with our observations in tissue.

conclusionsWe identified high performance methylated DNA marker panels for detection of CC. This knowledge has set the stage for development and implementation of novel, automated, self-contained CC detection assays in tissue and blood which can expeditiously and accurately detect colon cancer in both developed and underdeveloped regions of the world, enabling optimal use of limited resources in low- and middle-income countries.

Indexed as

AdultAgedAged, 80 and overBiomarkers, TumorColonic NeoplasmsDNA MethylationFemaleGenetic TestingHumansMaleMiddle AgedBiomarkers, TumorcMethDNAColon adenocarcinomaDetectionLiquid biopsyMethylationQM-MSP

Identifiers

PMID34903270
PMCPMC8670296
OpenAlexW4200224222

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.