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非洲裔胰腺导管腺癌患者的血清代谢组学和脂蛋白分析

Serum Metabolomic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry.

作者信息

Elebo Nnenna, Omoshoro-Jones Jones, Fru Pascaline N, Devar John, De Wet van Zyl Christiaan, Vorster Barend Christiaan, Smith Martin, Cacciatore Stefano, Zerbini Luiz F, Candy Geoffrey, Nweke Ekene Emmanuel

机构信息

Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.

Hepatopancreatobiliary Unit, Department of Surgery, Chris Hani-Baragwanath Academic Hospital, Johannesburg 1864, South Africa.

出版信息

Metabolites. 2021 Sep 28;11(10):663. doi: 10.3390/metabo11100663.

DOI:10.3390/metabo11100663
PMID:34677378
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8540259/
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman's correlation and Kapan Meier tests were conducted for correlation and survival analyses, respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose and lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used to predict patient survival and inform treatment intervention.

摘要

胰腺导管腺癌(PDAC)是一种具有特征性代谢失调的致命癌症。与代谢和炎症反应途径缺陷相关的异常临床病理特征可诱导PDAC的发生和发展。在本研究中,我们调查了非洲裔PDAC患者的代谢物和脂蛋白谱。对来自同意参与的个体(34例PDAC患者、6例慢性胰腺炎患者和6例健康参与者)的血清进行了核磁共振(NMR)光谱分析。从每个NMR光谱中定量了75个信号。使用Liposcale测试对脂蛋白进行表征。分别进行Spearman相关性分析和Kapan Meier测试以进行相关性分析和生存分析。在我们的患者队列中,结果表明糖酵解途径中涉及的代谢物水平随肿瘤分期增加。无论肿瘤分期如何,乙醇和3-羟基丁酸水平升高均与患者较短的生存时间独立相关。此外,胆红素水平升高导致PDAC患者脂蛋白谱异常。此外,我们观察到一组代谢物(如葡萄糖和乳酸)和脂蛋白的水平与炎症标志物的水平相关。综上所述,代谢表型有助于区分PDAC的严重程度,并可用于预测患者生存情况及指导治疗干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd60/8540259/eae965639e32/metabolites-11-00663-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd60/8540259/ce51bdaaa4a0/metabolites-11-00663-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd60/8540259/a89e66449826/metabolites-11-00663-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd60/8540259/5938e7cbb42c/metabolites-11-00663-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd60/8540259/36e8884ed27d/metabolites-11-00663-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd60/8540259/eae965639e32/metabolites-11-00663-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd60/8540259/ce51bdaaa4a0/metabolites-11-00663-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd60/8540259/a89e66449826/metabolites-11-00663-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd60/8540259/5938e7cbb42c/metabolites-11-00663-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd60/8540259/36e8884ed27d/metabolites-11-00663-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd60/8540259/eae965639e32/metabolites-11-00663-g005.jpg

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