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Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank
Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden.
Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden.
Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden ; Department of Clinical Sciences/Obstetrics and Gynecology, Umeå University, Sweden.
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]
Pancreatic neoplasms, biomarkers, hyperglycemia, risk, survival
National Category
Cancer and Oncology
Research subject
Bioinformatics
Identifiers
URN: urn:nbn:se:his:diva-23791DOI: 10.21037/jgo-23-930ISI: 001284655300018PubMedID: 38756646Scopus ID: 2-s2.0-85192826642OAI: oai:DiVA.org:his-23791DiVA, id: diva2:1855303
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-643451Region Västerbotten, RV-930478Region Västerbotten, RV-930132Region Västerbotten, RV-9960708Region Västerbotten, RV-99607108Region Västerbotten, VLL-837731Sjöberg FoundationBengt Ihres Foundation, SLS-885861Bengt Ihres Foundation, SLS-960529Swedish Society of Medicine, SLS-960379Lions Cancerforskningsfond i NorrKnut and Alice Wallenberg FoundationThe Kempe Foundations
Note

CC BY-NC-ND 4.0 DEED

Correspondence to: Emmy Borgmästars, PhD. Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Norrlands Universitetssjukhus, 6M, M31, 901 85 Umeå, Sweden. Email: emmy.borgmastars@umu.se

This work was supported by Umeå University, the Swedish Cancer Society (19 0273, 2017-557, CAN 2017/332, CAN 2017/827), the Swedish Research Council (2019-01690, 2016-02990, 2017-01531), Västerbotten Region (RV-583411, RV-549731, RV-841551, RV-930167, VLL-643451, RV-930478, RV-930132, RV-9960708, RV-99607108, VLL-837731), the Sjöberg Foundation, the Claes Groschinsky Memorial Foundation (M 19391), Bengt Ihre Foundation (SLS-885861, SLS-960529), Swedish Society of Medicine (SLS-960379), Lion’s Cancer Research Foundation, the Knut and Alice Wallenberg Foundation, Finska Läkaresällskapet, the Sigrid Juselius Foundation, Medicinska Understödsföreningen Liv och Hälsa, Bengt Ihre Fellowship Research Grant, and the JC Kempe Memorial Foundation Scholarship Fund.

Available from: 2024-04-30 Created: 2024-04-30 Last updated: 2024-08-15Bibliographically approved

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