Multi-omics profiling to identify early plasma biomarkers in pre-diagnostic pancreatic ductal adenocarcinoma: a nested case-control studyShow others and affiliations
2024 (English)In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 48, article id 102059
Article in journal (Refereed) Published
Abstract [en]
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor survival. Novel biomarkers are urgently needed to improve the outcome through early detection. Here, we aimed to discover novel biomarkers for early PDAC detection using multi-omics profiling in pre-diagnostic plasma samples biobanked after routine health examinations.
A nested case-control study within the Northern Sweden Health and Disease Study was designed. Pre-diagnostic plasma samples from 37 future PDAC patients collected within 2.3 years before diagnosis and 37 matched healthy controls were included. We analyzed metabolites using liquid chromatography mass spectrometry and gas chromatography mass spectrometry, microRNAs by HTG edgeseq, proteins by multiplex proximity extension assays, as well as three clinical biomarkers using milliplex technology. Supervised and unsupervised multi-omics integration were performed as well as univariate analyses for the different omics types and clinical biomarkers. Multiple hypothesis testing was corrected using Benjamini-Hochberg's method and a false discovery rate (FDR) below 0.1 was considered statistically significant.
Carbohydrate antigen (CA) 19-9 was associated with PDAC risk (OR [95 % CI] = 3.09 [1.31–7.29], FDR = 0.03) and increased closer to PDAC diagnosis. Supervised multi-omics models resulted in poor discrimination between future PDAC cases and healthy controls with obtained accuracies between 0.429–0.500. No single metabolite, microRNA, or protein was differentially altered (FDR < 0.1) between future PDAC cases and healthy controls.
CA 19-9 levels increase up to two years prior to PDAC diagnosis but extensive multi-omics analysis including metabolomics, microRNAomics and proteomics in this cohort did not identify novel early biomarkers for PDAC.
Place, publisher, year, edition, pages
Elsevier, 2024. Vol. 48, article id 102059
Keywords [en]
Pancreatic neoplasms, miRNomics, Metabolomics, Proteomics, Risk
National Category
Cancer and Oncology Bioinformatics and Computational Biology Bioinformatics (Computational Biology)
Research subject
Bioinformatics
Identifiers
URN: urn:nbn:se:his:diva-24392DOI: 10.1016/j.tranon.2024.102059ISI: 001272983200001PubMedID: 39018772Scopus ID: 2-s2.0-85198543877OAI: oai:DiVA.org:his-24392DiVA, id: diva2:1884505
Funder
Region VästerbottenSwedish Cancer Society, CAN 2016/643, 19 0273Swedish Research Council, 2016-02990, 2019-01690Sjöberg FoundationUmeå UniversityThe Royal Swedish Academy of Sciences, LM2021-0010, LM2023-0012Swedish Society of Medicine, SLS-960379Bengt Ihres Foundation, SLS-960529, SLS-986656
Note
CC BY 4.0
Corresponding author at: University Hospital of Umeå, 901 85 Umeå, Sweden. E-mail address: emmy.borgmastars@umu.se (E. Borgmästars)
The authors thank Hanna Nyström, and Daniel Öhlund at Umeå University for valuable assistance in data collection. We thank Xiaoshuang Feng at International Agency for Research of Cancer, Lyon, France for guidance in statistical analyses. The authors would also like to thank Swedish Metabolomics Centre, Umeå, Sweden (www.swedishmetabolomicscentre.se) and Biobanken Norr. Funding: This study was funded by Umeå University, the Swedish Research Council [2016-02990, 2019-01690], the Swedish Cancer Society [CAN 2016/643, 19 0273], Region Västerbotten [RV-583411, RV-549731, RV-583411, RV-841551, RV 967602], Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, the Sjöberg Foundation, The JC Kempe Memorial Foundation Scholarship Fund, The Royal Swedish Academy of Sciences (PE Lindahl Foundation, LM2021-0010 and LM2023-0012), The Swedish Society of Medicine (SLS-960379), Cancerforskningsfonden i Norrland (LP 23-2337), Bengt Ihre foundation (SLS-960529 and SLS-986656), and Bengt Ihre Research Fellowship Grant. The sponsors had no role in the study design, collection, analysis and interpretation of data, writing of the report, or in the decision to submit the article for publication.
2024-07-172024-07-172025-02-05Bibliographically approved