This study aimed to investigate the metabolite differences between patients with keratoconus and control subjects and identify potential serum biomarkers for keratoconus using a non-targeted metabolomics approach. Venous blood samples were obtained from patients with keratoconus (n = 20) as well as from age-, gender- and race-matched control subjects (n = 20). Metabolites extracted from serum were separated and analyzed by liquid chromatography/quadrupole time-of-flight mass spectrometer. Processing of raw data and analysis of the data files was performed using Agilent Mass Hunter Qualitative software. The identified metabolites were subjected to a principal component and hierarchical cluster analysis. Appropriate statistical tests were used to analyze the metabolomic profiling data. Together, the analysis revealed that the dehydroepiandrosterone sulfate from the steroidal hormone synthesis pathway was significantly upregulated in patients with keratoconus (p < 0.05). Also, a combination of eicosanoids from the arachidonic acid pathway, mainly prostaglandin F2α, prostaglandin A2, 16,16-dimethyl prostaglandin E2, and 5-hydroxyeicosatetraenoic acid were collectively up-regulated as a group in keratoconus patients (p < 0.05). On the other hand, glycerophospholipid PS(17:2(9Z,12Z)/20:4(5Z,8Z,11Z,14Z)) was found to be significantly upregulated in the metabolomics profiles of control subjects (p < 0.05). The differently regulated metabolites provide insights into the pathophysiology of keratoconus and could potentially be used as biomarkers for keratoconus to aid in screening for individuals at risk hence, enabling early diagnosis and timely monitoring of disease.

本研究旨在调查圆锥角膜患者和对照受试者之间的代谢物差异，并使用非靶向代谢组学方法确定圆锥角膜的潜在血清生物标志物。静脉血样本来自圆锥角膜患者 ( n  = 20) 以及年龄、性别和种族匹配的对照受试者 ( n = 20）。从血清中提取的代谢物通过液相色谱/四极杆飞行时间质谱仪进行分离和分析。使用 Agilent Mass Hunter 定性软件处理原始数据和分析数据文件。对鉴定的代谢物进行主成分和层次聚类分析。使用适当的统计测试来分析代谢组学分析数据。总之，分析表明，来自甾体激素合成途径的硫酸脱氢表雄酮在圆锥角膜患者中显着上调（p < 0.05)。此外，来自花生四烯酸途径的类二十烷酸的组合，主要是前列腺素 F2α、前列腺素 A2、16,16-二甲基前列腺素 E2 和 5-羟基二十碳四烯酸在圆锥角膜患者中作为一组共同上调（p  < 0.05）。另一方面，发现甘油磷脂 PS(17:2(9Z,12Z)/20:4(5Z,8Z,11Z,14Z)) 在对照受试者的代谢组学特征中显着上调 ( p  < 0.05)。不同调控的代谢物有助于深入了解圆锥角膜的病理生理学，并有可能用作圆锥角膜的生物标志物，以帮助筛查有风险的个体，从而实现疾病的早期诊断和及时监测。