Maity, Alok K;
Stone, Timothy C;
Ward, Vanessa;
Webster, Amy P;
Yang, Zhen;
Hogan, Aine;
McBain, Hazel;
... Lovat, Laurence B; + view all
(2022)
Novel epigenetic network biomarkers for early detection of esophageal cancer.
Clinical Epigenetics
, 14
(1)
, Article 23. 10.1186/s13148-022-01243-5.
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Abstract
BACKGROUND: Early 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. RESULTS: Here 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. CONCLUSIONS: Given 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.
| Type: | Article |
|---|---|
| Title: | Novel epigenetic network biomarkers for early detection of esophageal cancer |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13148-022-01243-5 |
| Publisher version: | https://doi.org/10.1186/s13148-022-01243-5 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Barrett’s esophagus, Biological networks, DNA methylation, Esophageal adenocarcinoma, Saliva, Single-cell RNA-Seq |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10143827 |
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