Epigenetic biomarkers in the progression of Barrett’s Oesophagus to oesophageal adenocarcinoma

Nieto, Thomas ORCID: 0000-0002-7280-9138 (2021). Epigenetic biomarkers in the progression of Barrett’s Oesophagus to oesophageal adenocarcinoma. University of Birmingham. Ph.D.

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Abstract

Introduction
Barrett’s Oesophagus (BO) represents a benign condition with no life limiting consequences. 0.33% of BO patients progress to oesophageal adenocarcinoma (OADC) which is a potentially catastrophic illness with high associated morbidity and mortality. If patients at high risk of progression to cancer could be identified, they could potentially be treated at an earlier disease stage.

Aims
To assess existing epigenetic biomarkers predicting progression from BO to OADC and validate the novel methylation biomarker OR3A4. Explore the functional relevance of OR3A4 and assess the immunological landscape of BO which progresses to OADC.

Methods
Genome wide methylation analysis and validation pyrosequencing of OR3A4 in BO tissue samples was performed. An OR3A4 over-expressing vector was transfected into BO and OADC cell lines and cell functional assays, total RNA sequencing and real time PCR was performed. Multispectral immunohistochemistry was performed to investigate the immunological landscape of BO.

Results
OR3A4 is hypomethylated in patients that progress from BO to OADC and OR3A4 over-expression has a functional effect in BO in vitro models and may contribute to immunological changes in BO tissues.

Conclusion
Hypomethylation of OR3A4 may provide a mechanism to explain the progression of
BO to OADC and predict progression of disease.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):