A unique urinary metabolomic signature for the detection of pancreatic ductal adenocarcinoma.
Autor: | Sahni S; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.; Australian Pancreatic Centre, Sydney, New South Wales, Australia., Pandya AR; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia., Hadden WJ; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia., Nahm CB; Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.; Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, New South Wales, Australia., Maloney S; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia., Cook V; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia., Toft JA; Nepean Clinical School, University of Sydney, New South Wales, Australia., Wilkinson-White L; Sydney Analytical Core Facility, University of Sydney, New South Wales, Australia., Gill AJ; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia., Samra JS; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Australian Pancreatic Centre, Sydney, New South Wales, Australia.; Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, New South Wales, Australia., Dona A; Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia., Mittal A; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.; Australian Pancreatic Centre, Sydney, New South Wales, Australia.; Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, New South Wales, Australia. |
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Jazyk: | angličtina |
Zdroj: | International journal of cancer [Int J Cancer] 2021 Mar 15; Vol. 148 (6), pp. 1508-1518. Date of Electronic Publication: 2020 Nov 12. |
DOI: | 10.1002/ijc.33368 |
Abstrakt: | Our study aimed to identify a urinary metabolite panel for the detection/diagnosis of pancreatic ductal adenocarcinoma (PDAC). PDAC continues to have poor survival outcomes. One of the major reasons for poor prognosis is the advanced stage of the disease at diagnosis. Hence, identification of a novel and cost-effective biomarker signature for early detection/diagnosis of PDAC could lead to better survival outcomes. Untargeted metabolomics was employed to identify a novel metabolite-based biomarker signature for PDAC diagnosis. Urinary metabolites from 92 PDAC patients (56 discovery cohort and 36 validation cohort) were compared with 56 healthy volunteers using 1 H nuclear magnetic resonance spectroscopy. Multivariate (partial-least squares discriminate analysis) and univariate (Mann-Whitney's U-test) analyses were performed to identify a metabolite panel which can be used to detect PDAC. The selected metabolites were further validated for their diagnostic potential using the area under the receiver operating characteristic (AUROC) curve. Statistical analysis identified a six-metabolite panel (trigonelline, glycolate, hippurate, creatine, myoinositol and hydroxyacetone), which demonstrated high potential to diagnose PDAC, with AUROC of 0.933 and 0.864 in the discovery and validation cohort, respectively. Notably, the identified panel also demonstrated very high potential to diagnose early-stage (I and II) PDAC patients with AUROC of 0.897. These results demonstrate that the selected metabolite signature could be used to detect PDAC and will pave the way for the development of a urinary test for detection/diagnosis of PDAC. (© 2020 Union for International Cancer Control.) |
Databáze: | MEDLINE |
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