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Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.ORCID iD: 0000-0001-9521-4463
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
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2024 (English)In: Journal of Gastrointestinal Oncology, ISSN 2078-6891, E-ISSN 2219-679X, Vol. 15, no 2, p. 755-767Article in journal (Refereed) Published
Abstract [en]

Background: Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.

Methods: We performed metabolomics by liquid and gas chromatography-mass spectrometry in plasma samples from 82 future pancreatic cancer patients and 82 matched healthy controls within the Northern Sweden Health and Disease Study (NSHDS). Logistic regression was used to assess univariate associations between metabolites and pancreatic cancer risk. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to design a metabolite-based risk score. We used receiver operating characteristic (ROC) analyses to assess the discriminative performance of the metabolite-based risk score.

Results: Among twelve risk-associated metabolites with a nominal P value <0.05, we defined a risk score of three metabolites [indoleacetate, 3-hydroxydecanoate (10:0-OH), and retention index (RI): 2,745.4] using LASSO. A logistic regression model containing these three metabolites, age, sex, body mass index (BMI), smoking status, sample date, fasting status, and carbohydrate antigen 19-9 (CA 19-9) yielded an internal area under curve (AUC) of 0.784 [95% confidence interval (CI): 0.714–0.854] compared to 0.681 (95% CI: 0.597–0.764) for a model without these metabolites (P value =0.007). Seventeen metabolites were significantly associated with pancreatic cancer survival [false discovery rate (FDR) <0.1].

Conclusions: Indoleacetate, 3-hydroxydecanoate (10:0-OH), and RI: 2,745.4 were identified as the top candidate biomarkers for early detection. However, continued efforts are warranted to determine the usefulness of these metabolites as early pancreatic cancer biomarkers.

Place, publisher, year, edition, pages
AME Publishing Company , 2024. Vol. 15, no 2, p. 755-767
Keywords [en]
biomarkers, hyperglycemia, Pancreatic neoplasms, risk, survival
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-224962DOI: 10.21037/jgo-23-930Scopus ID: 2-s2.0-85192826642OAI: oai:DiVA.org:umu-224962DiVA, id: diva2:1861275
Funder
Umeå UniversitySwedish Cancer Society, 19 0273Swedish Cancer Society, 2017-557Swedish Cancer Society, CAN 2017/332Swedish Cancer Society, CAN 2017/827Swedish Research Council, 2019-01690Swedish Research Council, 2016-02990Swedish Research Council, 2017-01531Region Västerbotten, RV-583411Region Västerbotten, RV-549731Region Västerbotten, RV-841551Region Västerbotten, RV-930167Region Västerbotten, VLL-643451Available from: 2024-05-27 Created: 2024-05-27 Last updated: 2024-05-27Bibliographically approved

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Borgmästars, EmmyJacobson, SaraSimm, MajaBilling, OlaLundin, ChristinaNyström, HannaÖhlund, DanielJonsson, PärFranklin, OskarSund, Malin

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Borgmästars, EmmyJacobson, SaraSimm, MajaBilling, OlaLundin, ChristinaNyström, HannaÖhlund, DanielJonsson, PärFranklin, OskarSund, Malin
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SurgeryObstetrics and GynecologyWallenberg Centre for Molecular Medicine at Umeå University (WCMM)OncologyDepartment of Chemistry
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Journal of Gastrointestinal Oncology
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