Background: Advances in mass spectrometry are providing new insights into the role of metabolomics in the aetiology of many diseases. Studies in retinopathy of prematurity (ROP), for instance, overlooked the role of metabolic alterations in disease development. Here, we employed comprehensive metabolic profiling and gold-standard metabolic analysis to explore major metabolites and metabolic pathways significantly affected in early stages of pathogenesis toward ROP. Methods: This is a multicentre, retrospective case-control study. We collected serums from 57 ROP cases and 57 strictly baseline matched non-ROP controls. Non-targeted ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) from Metabolon, Inc. was used to detect the metabolites in serum samples. Machine learning was used to unravel most affected metabolites and pathways in ROP development. Results: Compared to non-ROP controls, we found a significant metabolic perturbation in the ROP serums, featured with an increase in lipid, nucleotide, carbohydrate metabolites and a lower level of peptides. Machine leaning helped to distinguish a cluster of metabolic pathways (glycometabolism, redox homeostasis, lipid metabolism and arginine pathway) that were strongly related to the development of ROP. In addition, we found that the severity of ROP was related to the level of creatinine and ribitol. Conclusion: In the current study, our results suggested a strong link between metabolic profiling and retinal neovascularization during ROP pathogenesis. These findings provided an insight into identifying novel metabolic biomarkers for ROP diagnosis and prevention.

中文翻译：

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比较分析揭示了早产儿视网膜病变的血清代谢物和代谢组学网络的新变化

背景：质谱技术的进步为代谢组学在许多疾病的病因学中的作用提供了新的见解。例如，早产儿视网膜病变（ROP）的研究忽视了代谢改变在疾病发展中的作用。在这里，我们采用了全面的代谢谱分析和金标准代谢分析，以探索在ROP发病机理的早期阶段受到显着影响的主要代谢物和代谢途径。方法：这是一项多中心，回顾性病例对照研究。我们从57例ROP病例和57例严格基线匹配的非ROP对照中收集了血清。使用Metabolon，Inc.的非靶向超高效液相色谱-串联质谱（UPLC-MS / MS）检测血清样品中的代谢物。机器学习被用来揭示ROP发育中最受影响的代谢物和途径。结果：与非ROP对照相比，我们在ROP血清中发现了明显的代谢紊乱，其特征在于脂质，核苷酸，碳水化合物代谢产物的增加和肽水平的降低。机器学习有助于区分与ROP的发展密切相关的一系列代谢途径（糖代谢，氧化还原稳态，脂质代谢和精氨酸途径）。此外，我们发现ROP的严重程度与肌酐和核糖醇的水平有关。结论：在当前的研究中，我们的研究结果提示ROP发病机理中代谢谱分析与视网膜新血管形成之间存在密切联系。