Discovery of novel biomarkers for atherosclerotic aortic aneurysm through proteomics-based assessment of disease progression
Discovery of novel biomarkers for atherosclerotic aortic aneurysm through proteomics-based assessment of disease progression
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DOI：
10.1038/s41598-020-63229-8
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发表时间：
2020-04-14
影响因子：
4.6
通讯作者：
Minamino, Naoto
中科院分区：
文献类型：
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作者：
Yagi, Hiroaki;Nishigori, Mitsuhiro;Minamino, Naoto
由于主动脉瘤（AAs）大多无症状，但破裂后死亡率高，因此其检测和进展评估是临床上重要的问题。为了发现AA的诊断生物标志物，我们对胸动脉粥样硬化AA（TAAA）患者的主动脉中膜进行了蛋白质组分析，比较了动脉瘤和正常组织区域之间的蛋白质水平。蛋白质组分析数据的层次聚类分析后，组织样品被分为三组，无论形态特征。该分类反映了病理学检查确定的疾病进展阶段。这种基于蛋白质组学的分期系统使我们能够识别比形态学分类系统更显着改变的蛋白质。在随后的数据分析中，选择尼曼-匹克病C2型蛋白（NPC 2）和胰岛素样生长因子结合蛋白7（IGFBP 7）作为AA的新生物标志物候选者，并与先前报道的生物标志物血小板反应蛋白1（THBS 1）进行比较。在TAAA和腹主动脉粥样硬化性AA患者中，NPC 2和IGFBP 7的血液浓度显著升高，而THBS 1水平降低。AA患者和健康对照的受试者工作特征分析显示，NPC 2和IGFBP 7的特异性和敏感性高于THBS 1。因此，NPC 2和IGFBP 7是用于AA的检测和进展评估的有希望的生物标志物。
Since aortic aneurysms (AAs) are mostly asymptomatic, but they have a high mortality rate upon rupture, their detection and progression evaluation are clinically important issues. To discover diagnostic biomarkers for AA, we performed proteome analysis of aortic media from patients with thoracic atherosclerotic AA (TAAA), comparing protein levels between the aneurysm and normal tissue areas. After hierarchical clustering analysis of the proteome analysis data, tissue samples were classified into three groups, regardless of morphological features. This classification was shown to reflect disease progression stage identified by pathological examination. This proteomics-based staging system enabled us to identify more significantly altered proteins than the morphological classification system. In subsequent data analysis, Niemann-Pick disease type C2 protein (NPC2) and insulin-like growth factor-binding protein 7 (IGFBP7) were selected as novel biomarker candidates for AA and were compared with the previously reported biomarker, thrombospondin 1 (THBS1). Blood concentrations of NPC2 and IGFBP7 were significantly increased, while THBS1 levels were decreased in TAAA and abdominal atherosclerotic AA patients. Receiver operating characteristic analysis of AA patients and healthy controls showed that NPC2 and IGFBP7 have higher specificity and sensitivity than THBS1. Thus, NPC2 and IGFBP7 are promising biomarkers for the detection and progression evaluation of AA.