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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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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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Published: Swansea 2021
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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first_indexed 2021-10-08T13:20:41Z
last_indexed 2021-10-09T03:23:17Z
id cronfa58274
recordtype RisThesis
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spelling 2021-10-08T14:42:50.2875689 v2 58274 2021-10-08 The Utility of a Novel Blood Based Biomarker in the Diagnosis of Pancreatic Cancer cc0af0d9a301d75bdd3f2d7f84bb4a15 LUCY NICHOLS LUCY NICHOLS true false 2021-10-08 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. E-Thesis Swansea 8 10 2021 2021-10-08 10.23889/SUthesis.58274 A selection of third party content is redacted or is partially redacted from this thesis due to copyright restrictions. COLLEGE NANME COLLEGE CODE Swansea University Jenkins, Gareth Doctoral Ph.D 2021-10-08T14:42:50.2875689 2021-10-08T14:17:35.8729659 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine LUCY NICHOLS 1 58274__21122__c68d39202219427f9cb9fdeacc69efe4.pdf Nichols_Lucy_E_PhD_Thesis_Final_Redacted.pdf 2021-10-08T14:33:07.8592689 Output 3442711 application/pdf Redacted version - open access true Copyright; The author, Lucy Ellen Nichols, 2021. true eng
title The Utility of a Novel Blood Based Biomarker in the Diagnosis of Pancreatic Cancer
spellingShingle The Utility of a Novel Blood Based Biomarker in the Diagnosis of Pancreatic Cancer
LUCY NICHOLS
title_short The Utility of a Novel Blood Based Biomarker in the Diagnosis of Pancreatic Cancer
title_full The Utility of a Novel Blood Based Biomarker in the Diagnosis of Pancreatic Cancer
title_fullStr The Utility of a Novel Blood Based Biomarker in the Diagnosis of Pancreatic Cancer
title_full_unstemmed The Utility of a Novel Blood Based Biomarker in the Diagnosis of Pancreatic Cancer
title_sort The Utility of a Novel Blood Based Biomarker in the Diagnosis of Pancreatic Cancer
author_id_str_mv cc0af0d9a301d75bdd3f2d7f84bb4a15
author_id_fullname_str_mv cc0af0d9a301d75bdd3f2d7f84bb4a15_***_LUCY NICHOLS
author LUCY NICHOLS
author2 LUCY NICHOLS
format E-Thesis
publishDate 2021
institution Swansea University
doi_str_mv 10.23889/SUthesis.58274
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description 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.
published_date 2021-10-08T04:14:40Z
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score 11.036706

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