Tissue and plasma metabolomics in oesophago-gastric carcinogenesis

Singhal, Rishi (2013). Tissue and plasma metabolomics in oesophago-gastric carcinogenesis. University of Birmingham. M.D.

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Abstract

Introduction
Oesophageal cancer has a poor prognosis. Early diagnosis and the use of chemotherapy and surgery for local disease are key to improving survival. This study was designed to see if plasma and tissue metabolic profiles could be used to identify oesophago-gastric malignancy, indicate the presence of unstable pre-malignant (Barrett’s) epithelium or predict response to chemotherapy.

Methods
Patients were recruited from University Hospitals Birmingham between May 2009 and March 2010. Nuclear Magnetic Resonance (NMR) metabolomics was performed on filtered plasma and extracted tissue samples.

Results
Some 258 participants were recruited. NMR metabolomics discriminated between normal, Barrett’s and neoplastic epithelium. Tissue levels of hypoxanthine were highest in oesophageal adenocarcinoma compared to adjacent normal mucosa. Levels in Barrett’s mucosa in the presence of cancer fell between normal and neoplastic mucosa. 3-hydroxybutyrate levels were elevated both in cancer tissues and plasma compared to controls. Plasma levels of 3-hydroxybutyrate were higher in patients with node positive and full thickness tumours compared to those who were node negative with early local disease.

Conclusion
NMR metabolomics identified metabolic profiles that characterized different histologic tissue types.
Metabolites involved in oesophageal carcinogenesis might influence diagnostic and management strategies in these patients.

Type of Work:

Thesis (Higher Doctorates > M.D.)

Award Type:

Higher Doctorates > M.D.

Supervisor(s):