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.

中文翻译：

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两种新型动脉粥样硬化主动脉瘤生物标志物 Profilin 1 和补体因子 D 的血清蛋白质组学鉴定和验证

需要可在血液测试中检测到的有效的主动脉瘤 (AA) 诊断生物标志物，因为 AA 的早期检测和破裂风险评估可以为药物治疗和预防性治疗提供见解。然而，已知的 AA 生物标志物缺乏临床诊断的特异性和可靠性。我们对动脉粥样硬化性胸部 AA (TAA) 患者和健康对照 (HC) 受试者的血清样本进行了蛋白质组分析，以确定 AA 的诊断生物标志物。血清样品被分离成低密度脂蛋白、高密度脂蛋白和蛋白质组分，并且主要蛋白质被去除。从三个部分中鉴定的蛋白质中，我们将候选生物标志物缩小到 TAA 患者和 HC 受试者之间所有部分中一致改变的蛋白质，并使用接收器评估了它们区分 TAA 患者和腹部 AA (AAA) 患者与 HC 受试者的能力操作特征（ROC）分析。为了进行临床验证，测量了同一机构生物库中注册的 TAA 和 AAA 患者的候选生物标志物血清浓度，并评估了他们的诊断能力。Profilin 1 (PFN1) 和补体因子 D (CFD) 在 TAA 和 HC 受试者之间的所有三个部分中显示出最具对比性的特征，并被选为候选生物标志物。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，这些蛋白质可以将 TAA 和 AAA 患者与 HC 受试者区分开来。在验证研究中，这些候选药物在 TAA 或 AAA 患者与对照患者之间表现出显着的浓度差异。PFN1和CFD在ROC分析中显示出足够的曲线下面积（AUC），并且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着差异。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；它们的组合可以增强它们的诊断性能。这些生物标志物可能有助于开发诊断系统来识别 AA 患者。