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甲状腺乳头状癌患者的血浆代谢产物分析:基于核磁共振的初步非靶向代谢组学研究

Plasma metabolites analysis of patients with papillary thyroid cancer: A preliminary untargeted H NMR-based metabolomics.

机构信息

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA.

出版信息

J Pharm Biomed Anal. 2024 Apr 15;241:115946. doi: 10.1016/j.jpba.2023.115946. Epub 2023 Dec 28.

Abstract

Metabolomics plays a crucial role in identifying molecular biomarkers that can differentiate pathological conditions. In the case of thyroid cancer, it is essential to accurately diagnose malignancy from benignity to avoid unnecessary surgeries. The objective of this research was to apply untargeted NMR-based metabolomics in order to identify metabolic biomarkers that can distinguish between plasma samples of patients with papillary thyroid cancer (PTC) and multinodular goiter (MNG), as well as PTC and healthy individuals. The study included a cohort of 55 patients who were divided into three groups: PTC (n=20), MNG (n=16), and healthy (n=19). Plasma samples were collected from all participants and subjected to H NMR spectroscopy. Differential metabolites were identified using chemometric pattern recognition algorithms. The obtained metabolic profile had the potential to differentiate PTC from healthy plasma, but not from MNG. In patients diagnosed with PTC, a total of 18 compounds were discovered, revealing elevated levels of leucine, lysine, and 4-acetamidobutyric acid, while acetate, proline, acetoacetate, 3-hydroxybutyrate, glutamate, pyruvate, cystine, glutathione, asparagine, ethanolamine, histidine, tyrosine, myo-inositol, and glycerol along with a lipid compound were found to be lower in comparison to those of healthy individuals. According to the area under the curve (AUC) of the receiver operating characteristic curve, this particular profile exhibited an impressive capability of 85% to discern PTC from healthy subjects (AUC=0.853, sensitivity=78.95, specificity=84.21). The utilization of the H NMR-based metabolomics approach revealed considerable promise in the identification of PTC from healthy plasma specimens. The modifications noticed in the plasma metabolites have the potential to act as practical biomarkers that are non-invasive and could suggest transformations in the metabolic profile of thyroid tumors.

摘要

代谢组学在识别能够区分病理状况的分子生物标志物方面发挥着至关重要的作用。在甲状腺癌的情况下,准确地区分良恶性以避免不必要的手术是至关重要的。本研究旨在应用非靶向基于 NMR 的代谢组学方法,以鉴定能够区分甲状腺乳头状癌(PTC)和多结节性甲状腺肿(MNG)患者的血浆样本以及 PTC 和健康个体的代谢生物标志物。该研究包括了一个由 55 名患者组成的队列,他们被分为三组:PTC(n=20)、MNG(n=16)和健康个体(n=19)。从所有参与者收集血浆样本,并进行 H NMR 光谱分析。使用化学计量模式识别算法鉴定差异代谢物。所获得的代谢谱有潜力区分 PTC 与健康血浆,但不能区分 PTC 与 MNG。在诊断为 PTC 的患者中,发现了总共 18 种化合物,表明亮氨酸、赖氨酸和 4-乙酰氨基丁酸水平升高,而乙酸盐、脯氨酸、乙酰乙酸盐、3-羟基丁酸、谷氨酸、丙酮酸、胱氨酸、谷胱甘肽、天冬酰胺、乙醇胺、组氨酸、酪氨酸、肌醇和甘油以及一种脂质化合物的水平较低与健康个体相比。根据接受者操作特征曲线(ROC)的曲线下面积(AUC),该特定谱图显示出令人印象深刻的能力,能够将 PTC 与健康受试者区分开来,AUC=0.853,敏感性=78.95,特异性=84.21。基于 H NMR 的代谢组学方法的应用在识别健康血浆样本中的 PTC 方面显示出了很大的潜力。在血浆代谢物中观察到的变化有可能作为实用的生物标志物,具有非侵入性,可以提示甲状腺肿瘤代谢谱的变化。

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