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Contemporary approaches to the diagnosis and management of Pancreatic Ductal adenocarcinoma, examining the role of biomarkers in aiding early diagnosis / MATTHEW MORTIMER

Swansea University Author: MATTHEW MORTIMER

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DOI (Published version): 10.23889/SUthesis.66243

Abstract

Whilst other cancers have seen improvements in survival over recent decades, Pancreatic Ductal Adenocarcinoma (PDAC) remains a disease with poor outcomes. At present no screening tests exist to detect pancreatic cancer at an early stage in the asymptomatic population. There is an increasing interest...

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Published: Swansea, Wales, UK 2024
Institution: Swansea University
Degree level: Doctoral
Degree name: M.D
Supervisor: Kanamarlapudi, Venkateswarlu ; Dunstan, Peter
URI: https://cronfa.swan.ac.uk/Record/cronfa66243
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spelling v2 66243 2024-05-02 Contemporary approaches to the diagnosis and management of Pancreatic Ductal adenocarcinoma, examining the role of biomarkers in aiding early diagnosis dd4f91dcf80a71161bbf34b00640144c MATTHEW MORTIMER MATTHEW MORTIMER true false 2024-05-02 Whilst other cancers have seen improvements in survival over recent decades, Pancreatic Ductal Adenocarcinoma (PDAC) remains a disease with poor outcomes. At present no screening tests exist to detect pancreatic cancer at an early stage in the asymptomatic population. There is an increasing interest in novel ways to detect pancreatic cancer at an earlier stage in the disease process when a potential cure is more likely to be achieved. A literature review was undertaken of the current understanding and management of this devastating disease, focussing on aetiology, current methods of cancer diagnosis and staging, and therapeutic options. A feasibility study was then undertaken to evaluate the diagnostic accuracy of a selection of novel candidate biomarkers to differentiate between plasma and urine obtained from participants with and without pancreatic cancer, comparing them with the current gold standard biomarker, Ca19-9, which is often used with a cut-off concentration of 37U/L. Enzyme-Linked-Immunosorbent Assay (ELISA) was used to quantify concentrations of Ca19-9, Thrombospondin-2 (THBS2) and Human Chitinase 3-like 1 (YKL-40). Samples were analysed using Fourier Transform Infrared (FTIR) spectroscopy, with the spectra of cancer and non-cancer specimens being compared, allowing a machine-learning diagnostic model to be created. In isolation, plasma Ca19-9 had the greatest ability to discriminate between cancer and non-cancer (AUC = 0.885). However, a multi-analyte panel (comprising plasma Ca19-9, plasma THBS2 and urinary THBS2) was found to have a greater diagnostic accuracy to discriminate between the 2 groups when compared to using the widely used Ca19-9 cut-off of 37U/L (83.33% vs 76.6%). A diagnostic model using FTIR spectroscopy had a diagnostic accuracy of >90%.Pancreatic cancer remains a disease with poor outcomes, but there are promising new strategies to diagnose patients at an earlier stage. The initial results from these investigations are promising, but require validation with a larger test cohort. E-Thesis Swansea, Wales, UK Pancreatic Cancer, Biomarkers, Diagnosis, Management 21 2 2024 2024-02-21 10.23889/SUthesis.66243 COLLEGE NANME COLLEGE CODE Swansea University Kanamarlapudi, Venkateswarlu ; Dunstan, Peter Doctoral M.D 2024-05-02T15:46:54.7578591 2024-05-02T15:08:52.8222208 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science MATTHEW MORTIMER 1 66243__30243__a53dc442abf346e19820d899adb7bfca.pdf Mortimer_Matthew_MD_Thesis_Final_Redacted_Signatures.pdf 2024-05-02T15:24:36.9589685 Output 3429951 application/pdf E-Thesis – open access true Copyright: The Author, Matthew Christopher McKay Mortimer, 2024. true eng
title Contemporary approaches to the diagnosis and management of Pancreatic Ductal adenocarcinoma, examining the role of biomarkers in aiding early diagnosis
spellingShingle Contemporary approaches to the diagnosis and management of Pancreatic Ductal adenocarcinoma, examining the role of biomarkers in aiding early diagnosis
MATTHEW MORTIMER
title_short Contemporary approaches to the diagnosis and management of Pancreatic Ductal adenocarcinoma, examining the role of biomarkers in aiding early diagnosis
title_full Contemporary approaches to the diagnosis and management of Pancreatic Ductal adenocarcinoma, examining the role of biomarkers in aiding early diagnosis
title_fullStr Contemporary approaches to the diagnosis and management of Pancreatic Ductal adenocarcinoma, examining the role of biomarkers in aiding early diagnosis
title_full_unstemmed Contemporary approaches to the diagnosis and management of Pancreatic Ductal adenocarcinoma, examining the role of biomarkers in aiding early diagnosis
title_sort Contemporary approaches to the diagnosis and management of Pancreatic Ductal adenocarcinoma, examining the role of biomarkers in aiding early diagnosis
author_id_str_mv dd4f91dcf80a71161bbf34b00640144c
author_id_fullname_str_mv dd4f91dcf80a71161bbf34b00640144c_***_MATTHEW MORTIMER
author MATTHEW MORTIMER
author2 MATTHEW MORTIMER
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publishDate 2024
institution Swansea University
doi_str_mv 10.23889/SUthesis.66243
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 - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description Whilst other cancers have seen improvements in survival over recent decades, Pancreatic Ductal Adenocarcinoma (PDAC) remains a disease with poor outcomes. At present no screening tests exist to detect pancreatic cancer at an early stage in the asymptomatic population. There is an increasing interest in novel ways to detect pancreatic cancer at an earlier stage in the disease process when a potential cure is more likely to be achieved. A literature review was undertaken of the current understanding and management of this devastating disease, focussing on aetiology, current methods of cancer diagnosis and staging, and therapeutic options. A feasibility study was then undertaken to evaluate the diagnostic accuracy of a selection of novel candidate biomarkers to differentiate between plasma and urine obtained from participants with and without pancreatic cancer, comparing them with the current gold standard biomarker, Ca19-9, which is often used with a cut-off concentration of 37U/L. Enzyme-Linked-Immunosorbent Assay (ELISA) was used to quantify concentrations of Ca19-9, Thrombospondin-2 (THBS2) and Human Chitinase 3-like 1 (YKL-40). Samples were analysed using Fourier Transform Infrared (FTIR) spectroscopy, with the spectra of cancer and non-cancer specimens being compared, allowing a machine-learning diagnostic model to be created. In isolation, plasma Ca19-9 had the greatest ability to discriminate between cancer and non-cancer (AUC = 0.885). However, a multi-analyte panel (comprising plasma Ca19-9, plasma THBS2 and urinary THBS2) was found to have a greater diagnostic accuracy to discriminate between the 2 groups when compared to using the widely used Ca19-9 cut-off of 37U/L (83.33% vs 76.6%). A diagnostic model using FTIR spectroscopy had a diagnostic accuracy of >90%.Pancreatic cancer remains a disease with poor outcomes, but there are promising new strategies to diagnose patients at an earlier stage. The initial results from these investigations are promising, but require validation with a larger test cohort.
published_date 2024-02-21T15:46:54Z
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