Evidence map›Paper›PMID 39083293›Full record

ArticleClinical and translational medicine2024

Single-molecule epiallelic profiling of DNA derived from routinely collected Pap specimens for noninvasive detection of ovarian cancer.

Christine M O'Keefe, Yang Zhao, Leslie M Cope, Chih-Ming Ho, Amanda N Fader, Rebecca Stone, James S Ferris, Anna Beavis, Kimberly Levinson, Stephanie Wethington and 4 more

Abstract read
In one paragraph

Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–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

3 citing papers in PubMed.

  1. 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

14 authors.

Christine M O'KeefeDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.ORCID 0000-0002-7166-6972
Yang ZhaoDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Leslie M CopeSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Chih-Ming HoGynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan.
Amanda N FaderDepartment of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Rebecca StoneDepartment of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
James S FerrisDepartment of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Anna BeavisDepartment of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Kimberly LevinsonDepartment of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Stephanie WethingtonDepartment of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Tian-Li WangSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Thomas R PisanicSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0001-5796-0836
Ie-Ming ShihSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Tza-Huei WangDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.

Funding

Treatment of HIV- and HIV+ Patients with HPV16+ CIN2/3 Using pNGLV4a-hCRTE6E7L2 DNA vaccine administered intramuscularly via electroporationP50CA098252 · NCI · JOHNS HOPKINS UNIVERSITY · PI TZYY-CHOOU WU · 2003 to 2026
$53.5M
Development of a low-cost epigenetic screening assay for Pap specimen-based detection of early-stage ovarian cancer in high-risk womenR01CA260628 · NCI · JOHNS HOPKINS UNIVERSITY · PI PISANIC II, THOMAS RUSSELL, SHIH, IE-MING · 2021 to 2025
$2.1M
A low-cost, multiplexed digital high resolution melt platform for DNA methylation-based detection and identification of cancers in liquid biopsiesR33CA272321 · NCI · JOHNS HOPKINS UNIVERSITY · PI PISANIC II, THOMAS RUSSELL, WANG, TZA-HUEI JEFF · 2022 to 2024
$1.2M
Honorable Tina Brozman FoundationNCI NIH HHS P50 CA098252NCI NIH HHS R01 CA260628NCI NIH HHS R33 CA272321NIH HHS 1R01CA260628NIH HHS P50CA22899NIH HHS R33CA272321-01
6 · The paper itself

Abstract

Recent advances in molecular analyses of ovarian cancer have revealed a wealth of promising tumour-specific biomarkers, including protein, DNA mutations and methylation; however, reliably detecting such alterations at satisfactorily high sensitivity and specificity through low-cost methods remains challenging, especially in early-stage diseases. Here we present PapDREAM, a new approach that enables detection of rare, ovarian-cancer-specific aberrations of DNA methylation from routinely-collected cervical Pap specimens. The PapDREAM approach employs a microfluidic platform that performs highly parallelized digital high-resolution melt to analyze locus-specific DNA methylation patterns on a molecule-by-molecule basis at or near single CpG-site resolution at a fraction (< 1/10th) of the cost of next-generation sequencing techniques. We demonstrate the feasibility of the platform by assessing intermolecular heterogeneity of DNA methylation in a panel of methylation biomarker loci using DNA derived from Pap specimens obtained from a cohort of 43 women, including 18 cases with ovarian cancer and 25 cancer-free controls. PapDREAM leverages systematic multidimensional bioinformatic analyses of locus-specific methylation heterogeneity to improve upon Pap-specimen-based detection of ovarian cancer, demonstrating a clinical sensitivity of 50% at 99% specificity in detecting ovarian cancer cases with an area under the receiver operator curve of 0.90. We then establish a logistic regression model that could be used to identify high-risk patients for subsequent clinical follow-up and monitoring. The results of this study support the utility of PapDREAM as a simple, low-cost screening method with the potential to integrate with existing clinical workflows for early detection of ovarian cancer. KEY POINTS: We present a microfluidic platform for detection and analysis of rare, heterogeneously methylated DNA within Pap specimens towards detection of ovarian cancer. The platform achieves high sensitivity (fractions <0.00005%) at a suitably low cost (∼$25) for routine screening applications. Furthermore, it provides molecule-by-molecule quantitative analysis to facilitate further study on the effect of heterogeneous methylation on cancer development.

Indexed as

DNA MethylationOvarian NeoplasmsAdultBiomarkers, TumorDNAFemaleHumansMiddle AgedPapanicolaou TestSensitivity and SpecificityBiomarkers, TumorDNAdigital meltDNA methylationmicrofluidicsovarian cancerPap smear

Identifiers

PMID39083293
PMCPMC11290349

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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.