Evidence map›Paper›PMID 35164838›Full record

ArticleClinical epigenetics2022

Novel epigenetic network biomarkers for early detection of esophageal cancer.

Alok K Maity, Timothy C Stone, Vanessa Ward, Amy P Webster, Zhen Yang, Aine Hogan, Hazel McBain, Margaraet Duku, Kai Man Alexander Ho, Paul Wolfson and 5 more

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

Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
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  8. Roles and regulation of δ-catenin in tumorigenesis and neuronal diseases.Frontiers in cell and developmental biology · 2025
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  9. Translational cancer research · 2024
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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

15 authors at 5 institutions in 2 countries.

Alok K MaityCAS Key Lab of Computational Biology, Shanghai Institute for Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
Timothy C StoneDivision of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.
Vanessa WardDivision of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.
Amy P WebsterUniversity of Exeter Medical School, University of Exeter, Exeter, UK.
Zhen YangKey Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Aine HoganDivision of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.
Hazel McBainDivision of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.
Margaraet DukuDivision of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.
Kai Man Alexander HoDivision of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.
Paul WolfsonDivision of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.
David G GrahamDivision of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.
SPIT Study Group
Stephan BeckUCL Cancer Institute, University College London, Gower Street, London, WC1E 6BT, UK.
Andrew E TeschendorffCAS Key Lab of Computational Biology, Shanghai Institute for Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China. aeteschendorff21@outlook.com.ORCID 0000-0001-7410-6527
Laurence B LovatDivision of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK. l.lovat@ucl.ac.uk.
University College London · GBUniversity College London Hospitals NHS Foundation Trust · GBShanghai Institute of Nutrition and Health · CNFudan University · CNUniversity of Exeter · GB

Funding

National Science Foundation of China 31771464National Science Foundation of China 31970632Wellcome Trust 203145Z/16/Z
6 · The paper itself

Abstract

backgroundEarly detection of esophageal cancer is critical to improve survival. Whilst studies have identified biomarkers, their interpretation and validity is often confounded by cell-type heterogeneity.

resultsHere we applied systems-epigenomic and cell-type deconvolution algorithms to a discovery set encompassing RNA-Seq and DNA methylation data from esophageal adenocarcinoma (EAC) patients and matched normal-adjacent tissue, in order to identify robust biomarkers, free from the confounding effect posed by cell-type heterogeneity. We identify 12 gene-modules that are epigenetically deregulated in EAC, and are able to validate all 12 modules in 4 independent EAC cohorts. We demonstrate that the epigenetic deregulation is present in the epithelial compartment of EAC-tissue. Using single-cell RNA-Seq data we show that one of these modules, a proto-cadherin module centered around CTNND2, is inactivated in Barrett's Esophagus, a precursor lesion to EAC. By measuring DNA methylation in saliva from EAC cases and controls, we identify a chemokine module centered around CCL20, whose methylation patterns in saliva correlate with EAC status.

conclusionsGiven our observations that a CCL20 chemokine network is overactivated in EAC tissue and saliva from EAC patients, and that in independent studies CCL20 has been found to be overactivated in EAC tissue infected with the bacterium F. nucleatum, a bacterium that normally inhabits the oral cavity, our results highlight the possibility of using DNAm measurements in saliva as a proxy for changes occurring in the esophageal epithelium. Both the CTNND2/CCL20 modules represent novel promising network biomarkers for EAC that merit further investigation.

Indexed as

Barrett EsophagusEsophageal NeoplasmsBiomarkersBiomarkers, TumorDisease ProgressionDNA MethylationEarly Detection of CancerEpigenesis, GeneticEpigenomicsHumansBiomarkersBiomarkers, TumorBarrett’s esophagusBiological networksDNA methylationEsophageal adenocarcinomaSalivaSingle-cell RNA-Seq

Identifiers

PMID35164838
PMCPMC8845366
OpenAlexW4212943986

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.