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Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics

通过非靶向代谢组学和转录组学发现人动脉粥样硬化性腹主动脉瘤的潜在生物标志物

Abstract

Abdominal aortic aneurysm (AAA) and atherosclerosis (AS) have considerable similarities in clinical risk factors and molecular pathogenesis. The aim of our study was to investigate the differences between AAA and AS from the perspective of metabolomics, and to explore the potential mechanisms of differential metabolites via integration analysis with transcriptomics. Plasma samples from 32 AAA and 32 AS patients were applied to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry (LC-MS). A total of 18 remarkably different metabolites were identified, and a combination of seven metabolites could potentially serve as a biomarker to distinguish AAA and AS, with an area under the curve (AUC) of 0.93. Subsequently, we analyzed both the metabolomics and transcriptomics data and found that seven metabolites, especially 2′-deoxy-d-ribose (2dDR), were significantly correlated with differentially expressed genes. In conclusion, our study presents a comprehensive landscape of plasma metabolites in AAA and AS patients, and provides a research direction for pathogenetic mechanisms in atherosclerotic AAA.

概要

目的

腹主动脉瘤(AAA)和动脉粥样硬化(AS)在临床危险因素和分子发病机制上有相当大的相似之处. 我们的研究旨在从代谢组学的角度研究AAA和AS之间的差异, 并通过与转录组学的整合分析探索差异代谢物的潜在机制.

创新点

从代谢组学的角度探究了AAA和AS之间的差异; 采用关联分析, 探究差异代谢物和差异基因的交互作用整合了代谢组学和转录组学.

方法

应用32例AAA和32例AS患者的血浆样本表征代谢物谱, 采用非靶向液相色谱质谱法(LC-MS), 探究AAA与AS之间代谢物水平的差异; 应用GEO数据集GSE57691, 探究AAA与AS之间基因表达的差异; 最后应用Spearman相关分析探究差异代谢物与差异基因之间的相关性.

结论

本研究共鉴定出18种显著差异代谢物, 其中7种代谢物的组合可能作为区分AAA和AS的生物标志物, 曲线下面积(AUC)为0.93. 通过整合代谢组学和转录组学数据, 发现这7种代谢物, 尤其是2′-脱氧-d-核糖(2dDR)与差异表达基因显著相关. 本研究提供了AAA和AS患者血浆代谢物的全面概况, 并为动脉粥样硬化性AAA的发病机制提供了研究方向.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos. 51890894, 81770481, and 82070492) and the Chinese Academy of Medical Sciences, Innovation Fund for Medical Sciences (CIFMS 2017-I2M-1-008). We thank Biotree (Shanghai, China) for assistance with LC-MS.

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Authors

Contributions

Lei JI and Siliang CHEN performed the experimental research and data analysis, wrote and edited the manuscript. Guangchao GU, Wei WANG, Jinrui Ren, Fang XU, Fangda LI, and Jianqiang WU collected the samples. Yuehong ZHENG, Dan YANG, Lei JI, and Siliang CHEN contributed to the study design, data analysis, writing and editing of the manuscript. All authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.

Corresponding author

Correspondence to Yuehong Zheng.

Ethics declarations

Lei JI, Siliang CHEN, Guangchao GU, Wei WANG, Jinrui REN, Fang XU, Fangda LI, Jianqiang WU, Dan YANG, and Yuehong ZHENG declare that they have no conflict of interest.

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975; as revised in 2008 (5). This study was approved by the Ethics Committee of the Peking Union Medical College Hospital, China (JS-2629). Informed consent was obtained from all patients for being included in the study. Additional informed consent was obtained from all patients for whom identifying information is included in this article.

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Ji, L., Chen, S., Gu, G. et al. Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics. J. Zhejiang Univ. Sci. B 22, 733–745 (2021). https://doi.org/10.1631/jzus.B2000713

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Key words

  • Abdominal aortic aneurysm (AAA)
  • Atherosclerosis (AS)
  • Untargeted metabolomics
  • Transcriptomics

关键词

  • 腹主动脉瘤(AAA)
  • 动脉粥样硬化(AS)
  • 非靶向代谢组学
  • 转录组学