Evidence map›Paper›PMID 32520974›Full record

ArticlePloS one2020

A novel sensitive detection method for DNA methylation in circulating free DNA of pancreatic cancer.

Keiko Shinjo, Kazuo Hara, Genta Nagae, Takayoshi Umeda, Keisuke Katsushima, Miho Suzuki, Yoshiteru Murofushi, Yuta Umezu, Ichiro Takeuchi, Satoru Takahashi and 7 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 6% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
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  3. 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

17 authors at 7 institutions in 1 country.

Keiko ShinjoDivision of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID 0000-0002-7797-6453
Kazuo HaraDepartment of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
Genta NagaeGenome Science Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Takayoshi UmedaGenome Science Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Keisuke KatsushimaDivision of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Miho SuzukiDivision of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yoshiteru MurofushiDivision of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yuta UmezuDepartment of Computer Science, Nagoya Institute of Technology, Nagoya, Japan.
Ichiro TakeuchiDepartment of Computer Science, Nagoya Institute of Technology, Nagoya, Japan.
Satoru TakahashiDepartment of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Yusuke OkunoCenter for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
Keitaro MatsuoDivision of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
Hidemi ItoDivision of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan.
Shoji TajimaLaboratory of Epigenetics, Institute for Protein Research, Osaka University, Osaka, Japan.
Hiroyuki AburataniGenome Science Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Kenji YamaoDepartment of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
Yutaka KondoDivision of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Nagoya University · JPAichi Cancer Center · JPThe University of Tokyo · JPNagoya Institute of Technology · JPNagoya City University · JPNagoya University Hospital · JPProtein Research Foundation · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite recent advances in clinical treatment, pancreatic cancer remains a highly lethal malignancy. In order to improve the survival rate of patients with pancreatic cancer, the development of non-invasive diagnostic methods using effective biomarkers is urgently needed. Here, we developed a highly sensitive method to detect DNA methylation in cell-free (cf)DNA samples based on the enrichment of methyl-CpG binding (MBD) protein coupled with a digital PCR method (MBD-ddPCR). Five DNA methylation markers for the diagnosis of pancreatic cancer were identified through DNA methylation microarray analysis in 37 pancreatic cancers. The sensitivity and specificity of the five markers were validated in another independent cohort of pancreatic cancers (100% and 100%, respectively; n = 46) as well as in The Cancer Genome Atlas data set (96% and 90%, respectively; n = 137). MBD-ddPCR analysis revealed that DNA methylation in at least one of the five markers was detected in 23 (49%) samples of cfDNA from 47 patients with pancreatic cancer. Further, a combination of DNA methylation markers and the KRAS mutation status improved the diagnostic capability of this method (sensitivity and specificity, 68% and 86%, respectively). Genome-wide MBD-sequencing analysis in cancer tissues and corresponding cfDNA revealed that more than 80% of methylated regions were overlapping; DNA methylation profiles of cancerous tissues and cfDNA significantly correlated with each other (R = 0.97). Our data indicate that newly developed MBD-ddPCR is a sensitive method to detect cfDNA methylation and that using five marker genes plus KRAS mutations may be useful for the detection of pancreatic cancers.

Indexed as

DNA MethylationAdenocarcinomaAdultAgedAged, 80 and overBiomarkers, TumorCell-Free Nucleic AcidsCpG IslandsEarly Detection of CancerFemaleHumansMaleMethyl-CpG-Binding Protein 2Middle AgedMutationPancreatic NeoplasmsBiomarkers, TumorCell-Free Nucleic AcidsKRAS protein, humanMethyl-CpG-Binding Protein 2Proto-Oncogene Proteins p21(ras)

Identifiers

PMID32520974
PMCPMC7286528
OpenAlexW3034065854

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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.