Novel epigenetic network biomarkers for early detection of esophageal cancer.

Autor: Maity AK; CAS 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., Stone TC; Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK., Ward V; Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK., Webster AP; University of Exeter Medical School, University of Exeter, Exeter, UK., Yang Z; Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China., Hogan A; Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK., McBain H; Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK., Duku M; Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK., Ho KMA; Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK., Wolfson P; Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK., Graham DG; Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.; Division of GI Services, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London, NW1 2BU, UK., Beck S; UCL Cancer Institute, University College London, Gower Street, London, WC1E 6BT, UK., Teschendorff AE; CAS 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., Lovat LB; Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK. l.lovat@ucl.ac.uk.; Division of GI Services, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London, NW1 2BU, UK. l.lovat@ucl.ac.uk.
Jazyk: angličtina
Zdroj: Clinical epigenetics [Clin Epigenetics] 2022 Feb 14; Vol. 14 (1), pp. 23. Date of Electronic Publication: 2022 Feb 14.
DOI: 10.1186/s13148-022-01243-5
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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