Metabolomics for early detection of Pancreatic Ductal Adenocarcinoma Recurrence

Metabolomics for early detection of Pancreatic Ductal Adenocarcinoma Recurrence

PhD project title and outline, including interdisciplinary dimension:
Metabolomics for early detection of Pancreatic Ductal Adenocarcinoma Recurrence

Background
Pancreatic ductal adenocarcinoma (PDAC) is the fifth commonest cause of cancer-related mortality in the UK and by 2030 will cause more deaths than breast cancer.  Early stage PDAC is treated with radical surgical resection but despite this aggressive surgery over two-thirds of these patients relapse and die of their disease.  There is a need to develop novel biomarkers to detect minimal residual or low volume disease in asymptomatic individuals so that effective intervention can be carried out at a curable stage.

We propose to perform a study of PDAC genomics, transcriptomics and metabolomics derived from 40 patients undergoing adjuvant chemotherapy for PDAC at the Northern Ireland Cancer Centre.  This study will fulfil the COFUND SPaRK ‘3i’ criteria in the following ways:

Interdisciplinary
Recent studies have identified a blood-based metabolomics profile able to differentiate early stage PDAC from benign cysts and chromic pancreatitis.[1]  The ESR will develop a metabolomic signature predictive of recurrence in resected PDAC in collaboration with Dr Brian Green (IFGFS, QUB).  All plasma samples will be analysed by mass spectrometry at the QUB Mass Spectometry Core Technology Unit.

Intersectoral
PDAC tumour samples will undergo transcriptional and mutational profiling in collaboration with Almac Diagnostics (Craigavon, UK).  An integrative multi-omic analysis will be performed to provide novel biological insights into the molecular and metabolic biology of PDAC thorough the unsupervised clustering of data and identification of subgroups.   The ESR will be seconded to Almac Diagnostics and closely involved in sample analysis.

International
The ESR will present their results at a leading international conference and validation samples will be obtained from the Cancer Research UK PRECISIONPanc research program and international collaborators.

In summary, we will develop a novel metabolomics biomarker to predict early recurrence in PDAC and through an integrative analysis will identify novel insights into PDAC biology.

Primary supervisor: Dr Richard Turkington (Medicine, Dentistry and Biomedical Sciences)
Secondary supervisor: Dr Brian Green (Biological Sciences)
External Partner/Organisation: Almac Diagnostics