In search of early biomarkers in pancreatic ductal adenocarcinoma using multi-omics and bioinformatics
Background: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive malignancy with a 5-year survival of 10 %. Surgery is the only curative treatment. Unfortunately, few patients are eligible for surgery due to late detection. Thus, we need ways to detect the disease at an earlier stage and for...
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Umeå universitet, Kirurgi
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ftumeauniv:oai:DiVA.org:umu-201158 2023-10-09T21:54:38+02:00 In search of early biomarkers in pancreatic ductal adenocarcinoma using multi-omics and bioinformatics På jakt efter tidiga biomarkörer i bukspottkörtelcancer med hjälp av multi-omik och bioinformatik Borgmästars, Emmy 2022 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-201158 eng eng Umeå universitet, Kirurgi Umeå : Umeå University Umeå University medical dissertations, 0346-6612 2211 orcid:0000-0001-9521-4463 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-201158 urn:isbn:978-91-7855-929-9 urn:isbn:978-91-7855-928-2 info:eu-repo/semantics/openAccess Pancreatic cancer microRNA functional analysis TPS miRNomics metabolomics proteomics plasma samples early detection risk survival Cancer and Oncology Cancer och onkologi Bioinformatics and Systems Biology Bioinformatik och systembiologi Doctoral thesis, comprehensive summary info:eu-repo/semantics/doctoralThesis text 2022 ftumeauniv 2023-09-22T13:56:25Z Background: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive malignancy with a 5-year survival of 10 %. Surgery is the only curative treatment. Unfortunately, few patients are eligible for surgery due to late detection. Thus, we need ways to detect the disease at an earlier stage and for that good screening biomarkers could be used. Previous studies have analyzed circulating analytes in prospective studies to identify early PDAC signals. One such class is microRNAs (miRNAs). MicroRNAs are non-coding RNAs of around 22 nucleotides that act as post- transcriptional regulators by interaction with messenger RNAs (mRNAs). The function of a miRNA can be elucidated by target prediction, to identify its potential targets, followed by enrichment analysis of the predicted targets. Challenges with this approach includes a lot of false positives being generated and that miRNAs can perform their role in a tissue- or disease-specific manner. Other classes of analytes that have previously been studied in prospective PDAC cohorts are metabolites and proteins. Aims: This thesis has three aims. First, to build a miRNA functional analysis pipeline with correlation support between miRNA and its predicted target genes. Second, to identify potential circulating biomarkers for early detection of PDAC using multi-omics. Third, to identify potential prognostic metabolites in a prospective PDAC cohort. Methods: We used publicly available data from the cancer genome atlas-pancreatic adenocarcinoma (TCGA-PAAD) and pre-diagnostic plasma samples from the Northern Sweden Health and Disease Study. We built a pipeline in R including miRNA, mRNA, and protein expression data from TCGA-PAAD for in silico miRNA functional analysis. Pre- diagnostic plasma samples from future PDAC patients as well as matched healthy controls were analyzed using multi- omics. Tissue polypeptide specific antigen (TPS) was analyzed by enzyme linked immunosorbent assay in 267 future PDAC samples and 320 healthy controls. Metabolomics and clinical biomarkers ... Doctoral or Postdoctoral Thesis Northern Sweden Umeå University: Publications (DiVA) Omik ENVELOPE(173.583,173.583,52.417,52.417) |
institution |
Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
Pancreatic cancer microRNA functional analysis TPS miRNomics metabolomics proteomics plasma samples early detection risk survival Cancer and Oncology Cancer och onkologi Bioinformatics and Systems Biology Bioinformatik och systembiologi |
spellingShingle |
Pancreatic cancer microRNA functional analysis TPS miRNomics metabolomics proteomics plasma samples early detection risk survival Cancer and Oncology Cancer och onkologi Bioinformatics and Systems Biology Bioinformatik och systembiologi Borgmästars, Emmy In search of early biomarkers in pancreatic ductal adenocarcinoma using multi-omics and bioinformatics |
topic_facet |
Pancreatic cancer microRNA functional analysis TPS miRNomics metabolomics proteomics plasma samples early detection risk survival Cancer and Oncology Cancer och onkologi Bioinformatics and Systems Biology Bioinformatik och systembiologi |
description |
Background: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive malignancy with a 5-year survival of 10 %. Surgery is the only curative treatment. Unfortunately, few patients are eligible for surgery due to late detection. Thus, we need ways to detect the disease at an earlier stage and for that good screening biomarkers could be used. Previous studies have analyzed circulating analytes in prospective studies to identify early PDAC signals. One such class is microRNAs (miRNAs). MicroRNAs are non-coding RNAs of around 22 nucleotides that act as post- transcriptional regulators by interaction with messenger RNAs (mRNAs). The function of a miRNA can be elucidated by target prediction, to identify its potential targets, followed by enrichment analysis of the predicted targets. Challenges with this approach includes a lot of false positives being generated and that miRNAs can perform their role in a tissue- or disease-specific manner. Other classes of analytes that have previously been studied in prospective PDAC cohorts are metabolites and proteins. Aims: This thesis has three aims. First, to build a miRNA functional analysis pipeline with correlation support between miRNA and its predicted target genes. Second, to identify potential circulating biomarkers for early detection of PDAC using multi-omics. Third, to identify potential prognostic metabolites in a prospective PDAC cohort. Methods: We used publicly available data from the cancer genome atlas-pancreatic adenocarcinoma (TCGA-PAAD) and pre-diagnostic plasma samples from the Northern Sweden Health and Disease Study. We built a pipeline in R including miRNA, mRNA, and protein expression data from TCGA-PAAD for in silico miRNA functional analysis. Pre- diagnostic plasma samples from future PDAC patients as well as matched healthy controls were analyzed using multi- omics. Tissue polypeptide specific antigen (TPS) was analyzed by enzyme linked immunosorbent assay in 267 future PDAC samples and 320 healthy controls. Metabolomics and clinical biomarkers ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Borgmästars, Emmy |
author_facet |
Borgmästars, Emmy |
author_sort |
Borgmästars, Emmy |
title |
In search of early biomarkers in pancreatic ductal adenocarcinoma using multi-omics and bioinformatics |
title_short |
In search of early biomarkers in pancreatic ductal adenocarcinoma using multi-omics and bioinformatics |
title_full |
In search of early biomarkers in pancreatic ductal adenocarcinoma using multi-omics and bioinformatics |
title_fullStr |
In search of early biomarkers in pancreatic ductal adenocarcinoma using multi-omics and bioinformatics |
title_full_unstemmed |
In search of early biomarkers in pancreatic ductal adenocarcinoma using multi-omics and bioinformatics |
title_sort |
in search of early biomarkers in pancreatic ductal adenocarcinoma using multi-omics and bioinformatics |
publisher |
Umeå universitet, Kirurgi |
publishDate |
2022 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-201158 |
long_lat |
ENVELOPE(173.583,173.583,52.417,52.417) |
geographic |
Omik |
geographic_facet |
Omik |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Umeå University medical dissertations, 0346-6612 2211 orcid:0000-0001-9521-4463 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-201158 urn:isbn:978-91-7855-929-9 urn:isbn:978-91-7855-928-2 |
op_rights |
info:eu-repo/semantics/openAccess |
_version_ |
1779318298336296960 |