Biobanking Group, Institute of Biomedical Chemistry, 10 Pogodinskaya Str., Bld. 8, 119121 Moscow, Russia.
Russian Medical Academy of Continuous Professional Education, Ophthalmology Department, 2/1 Barrikadnaya Str., Bld. 1, 125993 Moscow, Russia.
Int J Mol Sci. 2022 Nov 24;23(23):14653. doi: 10.3390/ijms232314653.
Tear samples collected from patients with central retinal vein occlusion (CRVO; n = 28) and healthy volunteers (n = 29) were analyzed using a proteomic label-free absolute quantitative approach. A large proportion (458 proteins with a frequency > 0.6) of tear proteomes was found to be shared between the study groups. Comparative proteomic analysis revealed 29 proteins (p < 0.05) significantly differed between CRVO patients and the control group. Among them, S100A6 (log (2) FC = 1.11, p < 0.001), S100A8 (log (2) FC = 2.45, p < 0.001), S100A9 (log2 (FC) = 2.08, p < 0.001), and mesothelin ((log2 (FC) = 0.82, p < 0.001) were the most abundantly represented upregulated proteins, and β2-microglobulin was the most downregulated protein (log2 (FC) = −2.13, p < 0.001). The selected up- and downregulated proteins were gathered to customize a map of CRVO-related critical protein interactions with quantitative properties. The customized map (FDR < 0.01) revealed inflammation, impairment of retinal hemostasis, and immune response as the main set of processes associated with CRVO ischemic condition. The semantic analysis displayed the prevalence of core biological processes covering dysregulation of mitochondrial organization and utilization of improperly or topologically incorrect folded proteins as a consequence of oxidative stress, and escalating of the ischemic condition caused by the local retinal hemostasis dysregulation. The most significantly different proteins (S100A6, S100A8, S100A9, MSLN, and β2-microglobulin) were applied for the ROC analysis, and their AUC varied from 0.772 to 0.952, suggesting probable association with the CRVO.
采用无标记绝对定量蛋白质组学方法分析了 28 例中心性视网膜静脉阻塞（CRVO）患者和 29 例健康志愿者的泪液样本。研究组之间存在大量共享的泪液蛋白质组（458 种蛋白质，出现频率>0.6）。比较蛋白质组学分析显示，CRVO 患者与对照组之间有 29 种蛋白质（p<0.05）存在显著差异。其中，S100A6（log2FC=1.11，p<0.001）、S100A8（log2FC=2.45，p<0.001）、S100A9（log2FC=2.08，p<0.001）和间皮素（mesothelin，log2FC=0.82，p<0.001）为上调最显著的蛋白质，β2-微球蛋白为下调最显著的蛋白质（log2FC=-2.13，p<0.001）。选择上调和下调的蛋白质来定制与定量特性相关的 CRVO 关键蛋白质相互作用图。定制的图谱（FDR<0.01）显示，炎症、视网膜止血功能障碍和免疫反应是与 CRVO 缺血状态相关的主要过程集。语义分析显示，核心生物过程普遍存在，包括线粒体组织的失调和氧化应激导致不正确或拓扑不正确折叠蛋白质的利用，以及局部视网膜止血功能障碍导致的缺血状况加剧。差异最显著的蛋白质（S100A6、S100A8、S100A9、MSLN 和β2-微球蛋白）用于 ROC 分析，其 AUC 从 0.772 到 0.952 不等，提示可能与 CRVO 相关。
