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.
Int J Cancer. 2021 Mar 15;148(6):1508-1518. doi: 10.1002/ijc.33368. Epub 2020 Nov 12.
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 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.
我们的研究旨在确定用于检测/诊断胰腺导管腺癌 (PDAC) 的尿代谢物谱。PDAC 的生存结果仍然很差。预后不佳的一个主要原因是诊断时疾病处于晚期。因此，确定一种新的、具有成本效益的生物标志物特征，用于 PDAC 的早期检测/诊断，可能会带来更好的生存结果。我们采用非靶向代谢组学来确定用于 PDAC 诊断的新型基于代谢物的生物标志物特征。使用 H 核磁共振波谱法比较了 92 例 PDAC 患者（56 例发现队列和 36 例验证队列）和 56 名健康志愿者的尿代谢物。采用多元（偏最小二乘判别分析）和单变量（Mann-Whitney U 检验）分析来确定可用于检测 PDAC 的代谢物谱。使用接受者操作特征 (AUROC) 曲线进一步验证所选代谢物的诊断潜力。统计分析确定了一个由六种代谢物组成的（六氢吡啶，甘醇酸，马尿酸，肌醇，肌苷和羟基丙酮）的代谢物谱，该谱在发现和验证队列中均具有很高的诊断 PDAC 的潜力，AUROC 分别为 0.933 和 0.864。值得注意的是，该鉴定的谱也具有很高的潜力来诊断早期（I 和 II）PDAC 患者，AUROC 为 0.897。这些结果表明，所选代谢物特征可用于检测 PDAC，并为开发用于 PDAC 检测/诊断的尿液检测方法铺平道路。
