Murakami Yusuke, Nishigori Mitsuhiro, Yagi Hiroaki, Osaki Tsukasa, Wakabayashi Masaki, Shirai Manabu, Son Cheol, Iba Yutaka, Minatoya Kenji, Kusano Kengo, Tomita Tsutomu, Ishibashi-Ueda Hatsue, Matsuda Hitoshi, Minamino Naoto
Fundamental Research Laboratory, Research and Development Division, Eiken Chemical Co., Ltd., 143 Nogi, Nogimachi, Shimotsuga-gun, Tochigi, 329-0114, Japan.
Omics Research Center, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan.
Proteome Sci. 2023 Aug 5;21(1):11. doi: 10.1186/s12953-023-00212-x.
Effective diagnostic biomarkers for aortic aneurysm (AA) that are detectable in blood tests are required because early detection and rupture risk assessment of AA can provide insights into medical therapy and preventive treatments. However, known biomarkers for AA lack specificity and reliability for clinical diagnosis.
We performed proteome analysis of serum samples from patients with atherosclerotic thoracic AA (TAA) and healthy control (HC) subjects to identify diagnostic biomarkers for AA. Serum samples were separated into low-density lipoprotein, high-density lipoprotein, and protein fractions, and the major proteins were depleted. From the proteins identified in the three fractions, we narrowed down biomarker candidates to proteins uniformly altered in all fractions between patients with TAA and HC subjects and evaluated their capability to discriminate patients with TAA and those with abdominal AA (AAA) from HC subjects using receiver operating characteristic (ROC) analysis. For the clinical validation, serum concentrations of biomarker candidates were measured in patients with TAA and AAA registered in the biobank of the same institute, and their capability for the diagnosis was evaluated.
Profilin 1 (PFN1) and complement factor D (CFD) showed the most contrasting profiles in all three fractions between patients with TAA and HC subjects and were selected as biomarker candidates. The PFN1 concentration decreased, whereas the CFD concentration increased in the sera of patients with TAA and AAA when compared with those of HC subjects. The ROC analysis showed that these proteins could discriminate patients with TAA and AAA from HC subjects. In the validation study, these candidates showed significant concentration differences between patients with TAA or AAA and controls. PFN1 and CFD showed sufficient area under the curve (AUC) in the ROC analysis, and their combination further increased the AUC. The serum concentrations of PFN1 and CFD also showed significant differences between patients with aortic dissection and controls in the validation study.
PFN1 and CFD are potential diagnostic biomarkers for TAA and AAA and measurable in blood samples; their diagnostic performance can be augmented by their combination. These biomarkers may facilitate the development of diagnostic systems to identify patients with AA.
由于主动脉瘤（AA）的早期检测和破裂风险评估可为医学治疗和预防措施提供依据，因此需要在血液检测中可检测到的有效的AA诊断生物标志物。然而，已知的AA生物标志物在临床诊断中缺乏特异性和可靠性。
我们对动脉粥样硬化性胸主动脉瘤（TAA）患者和健康对照（HC）受试者的血清样本进行蛋白质组分析，以鉴定AA的诊断生物标志物。血清样本被分离为低密度脂蛋白、高密度脂蛋白和蛋白质组分，并去除主要蛋白质。从这三个组分中鉴定出的蛋白质中，我们将生物标志物候选物缩小到在TAA患者和HC受试者之间所有组分中均一致改变的蛋白质，并使用受试者工作特征（ROC）分析评估它们区分TAA患者和腹主动脉瘤（AAA）患者与HC受试者的能力。为了进行临床验证，在同一研究所生物样本库中登记的TAA和AAA患者中测量生物标志物候选物的血清浓度，并评估其诊断能力。
肌动蛋白结合蛋白1（PFN1）和补体因子D（CFD）在TAA患者和HC受试者之间的所有三个组分中表现出最显著的差异，并被选为生物标志物候选物。与HC受试者相比，TAA和AAA患者血清中PFN1浓度降低，而CFD浓度升高。ROC分析表明，这些蛋白质可以区分TAA和AAA患者与HC受试者。在验证研究中，这些候选物在TAA或AAA患者与对照组之间显示出显著的浓度差异。PFN1和CFD在ROC分析中显示出足够的曲线下面积（AUC），它们的组合进一步增加了AUC。在验证研究中，主动脉夹层患者和对照组之间的PFN1和CFD血清浓度也显示出显著差异。
PFN1和CFD是TAA和AAA的潜在诊断生物标志物，可在血液样本中测量；它们的组合可提高其诊断性能。这些生物标志物可能有助于开发诊断系统以识别AA患者。
