PDF(Pubmed)
Abstract：
UNASSIGNED: Proteomic studies investigating novel molecular markers of coronary artery calcification (CAC) are scarce.This study compared the protein expression in the serum of patients with severe CAC and non-CAC.
UNASSIGNED: The serum from 30 patients with severe CAC and 30 matched-controls were screened by data-independent acquisition(DIA)-based proteomic technology. Bioinformatics analysis tools were used to analyze the underlying molecular mechanisms of the differentially expressed proteins. Candidate proteins were further validated by an enzyme-linked immunosorbent assay (ELISA) in an independent cohort. A receiver operating characteristic (ROC) curve was used to estimate the diagnostic power of the candidate proteins.
UNASSIGNED: Among the 110 identified proteins, the expression of 81 was significantly upregulated, whereas 29 proteins were downregulated (fold change ≥ 1.5; p < 0.05) between patients with and without CAC. Bioinformatics analysis indicated that the differential proteins are involved in complement and coagulation cascades, platelet activation, regulation of actin cytoskeleton, or glycolysis/gluconeogenesis pathways. Further verification showed that serum levels of complement C5 (C5), fibrinogen gamma (FGG), pyruvate kinase isoform M2 (PKM2), and tropomyosin 4 (TPM4) were consistent with the proteomic findings, which could allow discrimination between CAC and non-CAC patients.
UNASSIGNED: This study revealed that high serum levels of serum C5, FGG, PKM2, and TPM4 proteins were linked to severe CAC. These proteins may be developed as biomarkers to predict coronary calcification.
UNASSIGNED: The serum from 30 patients with severe CAC and 30 matched-controls were screened by data-independent acquisition(DIA)-based proteomic technology. Bioinformatics analysis tools were used to analyze the underlying molecular mechanisms of the differentially expressed proteins. Candidate proteins were further validated by an enzyme-linked immunosorbent assay (ELISA) in an independent cohort. A receiver operating characteristic (ROC) curve was used to estimate the diagnostic power of the candidate proteins.
UNASSIGNED: Among the 110 identified proteins, the expression of 81 was significantly upregulated, whereas 29 proteins were downregulated (fold change ≥ 1.5; p < 0.05) between patients with and without CAC. Bioinformatics analysis indicated that the differential proteins are involved in complement and coagulation cascades, platelet activation, regulation of actin cytoskeleton, or glycolysis/gluconeogenesis pathways. Further verification showed that serum levels of complement C5 (C5), fibrinogen gamma (FGG), pyruvate kinase isoform M2 (PKM2), and tropomyosin 4 (TPM4) were consistent with the proteomic findings, which could allow discrimination between CAC and non-CAC patients.
UNASSIGNED: This study revealed that high serum levels of serum C5, FGG, PKM2, and TPM4 proteins were linked to severe CAC. These proteins may be developed as biomarkers to predict coronary calcification.
摘要：
■研究冠状动脉钙化（CAC）的新型分子标志物的蛋白质组学研究很少。本研究比较了重症CAC和非CAC患者血清中的蛋白表达。
■通过基于数据非依赖性采集（DIA）的蛋白质组学技术筛选了30例严重CAC患者和30例匹配对照的血清。生物信息学分析工具用于分析差异表达蛋白质的潜在分子机制。在独立队列中通过酶联免疫吸附测定(ELISA)进一步验证候选蛋白。受试者工作特征（ROC）曲线用于评估候选蛋白质的诊断能力。
■在110种鉴定的蛋白质中，81的表达显著上调，而有和没有CAC的患者中有29种蛋白质下调（倍数变化≥1.5；p<0.05）。生物信息学分析表明，差异蛋白参与补体和凝血级联反应，血小板活化,肌动蛋白细胞骨架的调节，或糖酵解/糖异生途径。进一步验证显示血清补体C5(C5)、纤维蛋白原γ（FGG），丙酮酸激酶同工型M2（PKM2），和原肌球蛋白4（TPM4）与蛋白质组学发现一致，这可以区分CAC和非CAC患者。
■这项研究表明，血清C5，FGG，PKM2和TPM4蛋白与严重CAC相关。这些蛋白质可以被开发为预测冠状动脉钙化的生物标志物。
■通过基于数据非依赖性采集（DIA）的蛋白质组学技术筛选了30例严重CAC患者和30例匹配对照的血清。生物信息学分析工具用于分析差异表达蛋白质的潜在分子机制。在独立队列中通过酶联免疫吸附测定(ELISA)进一步验证候选蛋白。受试者工作特征（ROC）曲线用于评估候选蛋白质的诊断能力。
■在110种鉴定的蛋白质中，81的表达显著上调，而有和没有CAC的患者中有29种蛋白质下调（倍数变化≥1.5；p<0.05）。生物信息学分析表明，差异蛋白参与补体和凝血级联反应，血小板活化,肌动蛋白细胞骨架的调节，或糖酵解/糖异生途径。进一步验证显示血清补体C5(C5)、纤维蛋白原γ（FGG），丙酮酸激酶同工型M2（PKM2），和原肌球蛋白4（TPM4）与蛋白质组学发现一致，这可以区分CAC和非CAC患者。
■这项研究表明，血清C5，FGG，PKM2和TPM4蛋白与严重CAC相关。这些蛋白质可以被开发为预测冠状动脉钙化的生物标志物。
