Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.569146
Title: Early detection of pancreatic cancer : use of genetic and proteomic approaches
Author: Murray, Seonaid Margaret
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2011
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Abstract:
Aims of the investigation The aims of this investigation were to detect pancreatic cancer earlier using both genetic and proteomic approaches. The aims of the genetic approach were to use Amplification Refractory Mutation System (ARMS) to detect KRAS mutations in blood serum and plasma, pancreatic juice and tissue from patients with pancreatic cancer, chronic pancreatitis and other benign disease controls. The aims of the proteomic approach were to use Isobaric Tags for Relative and Absolute Quantification (iTRAQ) to identify and quantify the proteins present in blood serum from patients with 'early' and 'later' stage pancreatic cancer, chronic pancreatitis and healthy controls. In this thesis 'early' stage pancreatic cancer was defined as patients with lymph node negative status while 'later' stage pancreatic cancer was defined as patients with lymph node positive status. Results achieved DNA extraction from blood serum and plasma, pancreatic juice and tissue was successful. DNA concentrations were higher in pancreatic juice compared with serum and plasma. DNA concentrations were higher in serum compared with plasma. KRAS mutations were detected in 71.7 % of pancreatic cancer patients in pancreatic juice samples, 51.9 % in serum samples, 45.1 % in plasma samples and 79 % in pancreatic tissue samples. KRAS mutations were detected in 42.9 % of chronic pancreatitis patients in pancreatic juice samples, 43.8 % in serum samples and 20 % in plasma samples. A total of 254 proteins were identified and 234 proteins were quantified using iTRAQ in serum from early and later stage pancreatic cancer patients, chronic pancreatitis patients and healthy controls. Of these proteins, 48 showed a greater than 3-fold change between the early stage pancreatic cancer group and controls. Of these proteins, three were selected for further analysis: von Willebrand Factor, Collagen I and Collagen Ill. Further validation using Western blotting and ELlSA verified the iTRAQ result for von Willebrand Factor that this protein was elevated in the early stage pancreatic cancer group compared with controls.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.569146  DOI: Not available
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