E-Thesis 211 views 109 downloads
The Utility of a Novel Blood Based Biomarker in the Diagnosis of Pancreatic Cancer / LUCY NICHOLS
Swansea University Author: LUCY NICHOLS
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PDF | Redacted version - open access
Copyright; The author, Lucy Ellen Nichols, 2021.
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DOI (Published version): 10.23889/SUthesis.58274
Abstract
Pancreatic cancer maintains one of the worst prognoses of all malignancies. Fewer than 1% of patients survive 10-years post-diagnosis. It is an aggressive disease with as many as 80% of patients diagnosed in the most advanced stages of disease. This severely limits treatment options, contributing to...
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Swansea
2021
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| Institution: | Swansea University |
| Degree level: | Doctoral |
| Degree name: | Ph.D |
| Supervisor: | Jenkins, Gareth |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa58274 |
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| Abstract: |
Pancreatic cancer maintains one of the worst prognoses of all malignancies. Fewer than 1% of patients survive 10-years post-diagnosis. It is an aggressive disease with as many as 80% of patients diagnosed in the most advanced stages of disease. This severely limits treatment options, contributing to the dismal prognosis. Diagnosis remains a challenge. Often, imaging alone cannot differentiate between benign or malignant disease. Blood-based biomarker CA19-9 cannot be relied upon since it is a modified Lewis antigen so 5-10% of the population do not express it. Tissue biopsies remain the gold-standard for final confirmed diagnoses, yet collection of pancreatic biopsies is invasive, time and resource intensive and have a range of risks associated. Blood-based biomarkers offer a less invasive, cheaper, and more accessible alternative to more traditional diagnostic techniques. Here, we explored the use of novel DNA mutation assay, the human erythrocyte PIG-A assay, as a blood-based biomarker to determine whether it had any potential in diagnosing pancreatic cancer. An elevated frequency of PIG-A mutant erythrocytes was observed within pancreatic cancer patients in comparison to controls of healthy donors and a benign pancreatic disease cohort. Furthermore, the more well-established human peripheral blood mononuclear cell cytokinesis block micronucleus assay provided a secondary measure of DNA damage. An elevation was also viewed in this assay in malignant donors. Both assays were additionally explored within an in vitro setting, modelling the induction of DNA damage by known risk factors for pancreatic cancer. Given the complexity of pancreatic cancer diagnosis, a panel of biomarkers was explored, combining clinical markers of inflammation with our two DNA-based biomarkers and clinically approved CA19-9. Combination of the novel PIG-A mutation assay and CA19-9 blood-test appeared the most suitable panel of biomarkers for future exploration. |
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| Item Description: |
A selection of third party content is redacted or is partially redacted from this thesis due to copyright restrictions. |
| College: |
Faculty of Medicine, Health and Life Sciences |