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Abstract：
Ectopia lentis is a hallmark of Marfan syndrome (MFS), a genetic connective tissue disorder affecting 1/5000 to 1/10 000 individuals worldwide. Early detection in ophthalmology clinics and timely intervention of cardiovascular complications can be lifesaving. In this study, a modified proteomics workflow with liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based data-independent acquisition (DIA) and field asymmetric ion mobility spectrometry (FAIMS) to profile the proteomes of aqueous humor (AH) and lens tissue from MFS children with ectopia lentis is utilized. Over 2300 and 2938 comparable proteins are identified in AH and the lens capsule, respectively. Functional enrichment analyses uncovered dysregulation of complement and coagulation-related pathways, collagen binding, and cell adhesion in MFS. Through weighted correlation network analysis (WGCNA) and machine learning, distinct modules associated with clinical traits are constructed and a unique biomarker panel (Q14376, Q99972, P02760, Q07507; gene names: GALE, MYOC, AMBP, DPT) is defined. These biomarkers are further validated using advanced parallel reaction monitoring (PRM) in an independent patient cohort. The results provide novel insights into the proteome characterization of ectopia lentis and offer a promising approach for developing a valuable biomarker panel to aid in the early diagnosis of Marfan syndrome via AH proteome.
摘要：
扁桃体是马凡氏综合症（MFS）的标志，一种影响全球1/5000至1/10000人的遗传性结缔组织疾病。在眼科诊所早期发现并及时干预心血管并发症可以挽救生命。在这项研究中,使用基于液相色谱-串联质谱（LC-MS/MS）的基于数据独立采集（DIA）和场不对称离子迁移谱（FAIMS）的改良蛋白质组学工作流程，以分析MFS儿童的房水（AH）和晶状体组织的蛋白质组。在AH和晶状体囊中鉴定出超过2300和2938种可比较的蛋白质，分别。功能富集分析发现补体和凝血相关途径的失调，胶原蛋白结合，和MFS中的细胞粘附。通过加权相关网络分析(WGCNA)和机器学习，构建了与临床特征相关的不同模块和独特的生物标志物组(Q14376，Q99972，P02760，Q07507；基因名称：GALE，MYOC,AMBP,DPT)定义。在独立患者队列中使用高级平行反应监测(PRM)进一步验证这些生物标志物。该结果提供了对扁桃体异位的蛋白质组表征的新见解，并为开发有价值的生物标志物小组提供了有希望的方法，以通过AH蛋白质组帮助马凡氏综合征的早期诊断。
