Serum Metabolomics Reveals Personalized Metabolic Patterns for Macular Neovascular Disease Patient Stratification

代谢组学 脉络膜新生血管 代谢组 黄斑变性 代谢途径 医学 黄斑病 磷酸戊糖途径 生物信息学 糖酵解 内科学 生物 视网膜病变 糖尿病 眼科 新陈代谢 内分泌学
作者
Kun Liu,Junwei Fang,Jin Jing,Shaopin Zhu,Xiaoyin Xu,Yupeng Xu,Bin Ye,Shuhai Lin,Xun Xu
出处
期刊:Journal of Proteome Research [American Chemical Society]
卷期号:19 (2): 699-707 被引量:19
标识
DOI:10.1021/acs.jproteome.9b00574
摘要

The macular neovascular disease is a group disorder with complex pathogenesis of neovascularization for vision impairment and irreversible blindness, posing great challenges to precise diagnosis and management. We prospectively recruited participants with age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), and pathological myopia (PM) and compared with cataract patients without fundus diseases as a control group. The serum metabolome was profiled by gas chromatography coupled with time-of-flight mass spectrometry (GC-TOFMS) analysis. Multivariate statistical methods as well as data mining were performed for interpretation of macular neovascularization. A total of 446 participants with macular neovascularization and 138 cataract subjects as the control group were enrolled in this study. By employing GC-TOFMS, 131 metabolites were identified and 33 differentiating metabolites were highlighted in patients with macular neovascularization. For differential diagnosis, three panels of specific metabolomics-based biomarkers provided areas under the curve of 0.967, 0.938, and 0.877 in the discovery phase (n = 328) and predictive values of 87.3%, 79%, and 85.7% in the test phase (n = 256). Personalized pathway dysregulation scores measurement using Lilikoi package in R language revealed the pentose phosphate pathway and mitochondrial electron transport chain as the most important pathways in AMD; purine metabolism and glycolysis were identified as the major disturbed pathways in PCV, while the altered thiamine metabolism and purine metabolism may contribute to PM phenotypes. Serum metabolomics are powerful for characterizing metabolic disturbances of the macular neovascular disease. Differences in metabolic pathways may reflect an underlying macular neovascular disease and serve as therapeutic targets for macular neovascular treatment.
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