The Genomic and Metabolomic profiling of pancreas cancer

Abstract

Despite the considerable expansion of knowledge in the development of pancreatic cancer, there has been little progress made in facilitating an early diagnosis of this disease and predicting an accurate response to treatment. We aim to translate this knowledge to clinical practice by using a prospective database of precursor cystic lesions in pancreas cancer, assessing the use of over-expressed genes in pancreatic juice as a surrogate marker of these pancreas cancer and finally, downstream of these changes at the genetic level, use metabolomic techniques to look for biomarkers in pancreas cancer in serum.In the first study, we investigate the natural history of pancreatic cystic neoplasms, specifically IPMNs, using a prospectively collected database to examine the profiles and outcomes of main duct IPMN, branch duct IPMN and cystic lesions measuring less than 3 cm in size. A total of 99 patients with suspected pancreatic cystic tumours were enrolled over 3 years. Median follow-up was 24 months (range 0 - 124). Cystic tumours comprised of 13 MD-IPMN, 40 BD-IPMN, 11 MCN and 8 adenocarcinomas among others. The complete cohort showed an overall risk of adenocarcinoma of 8%. Main duct IPMN showed a cumulative risk of 46% with evidence of progression of disease in a further 23%. The associated mortality in MD-IPMN was related to the underlying adenocarcinoma and was 38% in our group. The incidence of adenocarcinoma in branch duct IPMN was 11% with disease progression seen 13.8%. Evidence of extra-pancreatic malignancies was seen in 37.7% of patients with IPMN. In the second study, we explore the feasibility of gene expression profiling from RNA isolated from matched pancreatic juice and tumour tissue in patients with pancreatic cancer and pancreatic cystic tumours. RNA was isolated and Poly(A) PCR was used to globally amplify the RNA. RT-PCR was used to measure expression levels of 18 genes common to both pancreas cancer and pancreatic cystic tumours. Spearman's rank correlation test was used to examine the relationship of gene expression between pancreatic juice and tissue. One gene out of eighteen, MSLN (p

Date of Award	1 Aug 2015
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Ajith Siriwardena (Supervisor) & Richard Byers (Supervisor)