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Serum Metabolomics Reveals Personalized Metabolic Patterns for Macular Neovascular Disease Patient Stratification.
Journal of Proteome Research ( IF 4.4 ) Pub Date : 2020-01-09 , DOI: 10.1021/acs.jproteome.9b00574
Kun Liu 1 , Junwei Fang 1, 2 , Jing Jin 1 , Shaopin Zhu 1 , Xiaoyin Xu 1 , Yupeng Xu 1 , Bin Ye 1 , Shu-Hai Lin 2, 3 , Xun Xu 1
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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.

中文翻译:

血清代谢组学揭示了针对黄斑新生血管疾病患者分层的个性化代谢模式。

黄斑部新血管疾病是一种因视力障碍和不可逆性失明而导致新血管形成的复杂发病机制的群体疾病,对精确的诊断和治疗提出了巨大的挑战。我们前瞻性招募了年龄相关性黄斑变性(AMD),息肉样脉络膜血管病(PCV)和病理性近视(PM)的参与者,并与无眼底疾病的白内障患者进行了比较。通过气相色谱结合飞行时间质谱(GC-TOFMS)分析对血清代谢组进行分析。进行了多变量统计方法以及数据挖掘,以解释黄斑部新生血管形成。本研究共纳入446名黄斑部新生血管参与者和138名白内障受试者作为对照组。通过使用GC-TOFMS,在黄斑部新生血管形成的患者中,鉴定出131种代谢物,并突出显示33种可区分的代谢物。为了进行鉴别诊断,三组基于特定代谢组学的生物标记物在发现阶段(n = 328)的曲线下面积分别为0.967、0.938和0.877,在测试阶段提供了87.3%,79%和85.7%的预测值(n = 256)。使用R语言的Lilikoi软件包进行的个性化通路失调评分测量显示,磷酸戊糖通路和线粒体电子转运链是AMD中最重要的通路。嘌呤代谢和糖酵解被认为是PCV的主要干扰途径,而硫胺素代谢和嘌呤代谢的改变可能是PM的表型。血清代谢组学对表征黄斑部新生血管疾病的代谢紊乱具有重要作用。代谢途径的差异可能反映了潜在的黄斑新生血管疾病,并成为黄斑新生血管治疗的治疗靶标。
更新日期:2020-01-10
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