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血清脂质组学分析揭示甲状腺功能障碍的生物标志物和代谢途径。

Serum Lipidomic Analysis Reveals Biomarkers and Metabolic Pathways of Thyroid Dysfunction.

作者信息

Dong Hua, Zhou Wenjie, Yan Xingxu, Zhao Huan, Zhao Honggang, Jiao Yan, Sun Guijiang, Li Yubo, Zhang Zuncheng

机构信息

Department of Nuclear Medicine, The Second Hospital of Tianjin Medical University, Tianjin 300211, China.

School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

出版信息

ACS Omega. 2023 Mar 7;8(11):10355-10364. doi: 10.1021/acsomega.2c08048. eCollection 2023 Mar 21.

DOI:10.1021/acsomega.2c08048
PMID:36969406
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10034973/
Abstract

Abnormal thyroid hormone secretion is the most important feature of hypothyroidism and plays an important role in lipid metabolism. However, their connection has not been clearly established. This study aimed to identify the serum biomarkers and metabolic pathways associated with hyperthyroidism and hypothyroidism. The study enrolled discovery and validation sets of 175 and 300 participants, respectively, to identify and validate the serum biomarkers of hyperthyroidism and hypothyroidism via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry lipidomics through univariate and multivariate analyses. Eight and six biomarkers were identified for hyperthyroidism and hypothyroidism, respectively. Spearman correlation analysis was used to assess the correlation between the biomarkers and thyroid dysfunction indicators; subsequently, metabolic pathway and network analyses were performed for these biomarkers. Most biomarkers exhibited significant correlation with thyroid dysfunction indicators, mainly being enriched in the glycerophospholipid (GPL) metabolism. The diagnostic accuracies of the biomarkers and biomarker panels were assessed via receiver operating characteristic curve analysis. All the biomarkers demonstrated good diagnostic performance, and the hyperthyroidism and hypothyroidism biomarker panels reached an area under the curve value of 1.000. The results were validated using the validation set. Therefore, our findings revealed that thyroid dysfunction primarily affects the human metabolism via the GPL metabolism, thus providing a theoretical basis for the clinical prevention and control of thyroid dysfunction.

摘要

甲状腺激素分泌异常是甲状腺功能减退症的最重要特征,并且在脂质代谢中起重要作用。然而,它们之间的联系尚未明确确立。本研究旨在确定与甲状腺功能亢进和甲状腺功能减退相关的血清生物标志物和代谢途径。该研究分别纳入了175名和300名参与者的发现集和验证集,通过超高效液相色谱 - 四极杆飞行时间质谱脂质组学,经单变量和多变量分析来识别和验证甲状腺功能亢进和甲状腺功能减退的血清生物标志物。分别为甲状腺功能亢进和甲状腺功能减退鉴定出了8种和6种生物标志物。采用Spearman相关性分析评估生物标志物与甲状腺功能障碍指标之间的相关性;随后,对这些生物标志物进行代谢途径和网络分析。大多数生物标志物与甲状腺功能障碍指标表现出显著相关性,主要富集于甘油磷脂(GPL)代谢。通过受试者工作特征曲线分析评估生物标志物和生物标志物组合的诊断准确性。所有生物标志物均表现出良好的诊断性能,甲状腺功能亢进和甲状腺功能减退的生物标志物组合的曲线下面积值达到1.000。使用验证集对结果进行了验证。因此,我们的研究结果表明,甲状腺功能障碍主要通过GPL代谢影响人体代谢,从而为甲状腺功能障碍的临床预防和控制提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/b2e2e8b709e5/ao2c08048_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/e1d43928d368/ao2c08048_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/6aa02704d28a/ao2c08048_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/071cd44dbda1/ao2c08048_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/51a887640d25/ao2c08048_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/bd1ac8e9f77e/ao2c08048_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/b2e2e8b709e5/ao2c08048_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/e1d43928d368/ao2c08048_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/6aa02704d28a/ao2c08048_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/071cd44dbda1/ao2c08048_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/51a887640d25/ao2c08048_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/bd1ac8e9f77e/ao2c08048_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0b6/10034973/b2e2e8b709e5/ao2c08048_0007.jpg

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