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医学代谢组学案例分析

通过GC-MS检测血液样本

分析哮喘病人的代谢物组信息变化


研究对象:人血

分析检测平台:GC-TOF/MS (BIOTREE)

期刊:Acta Pharmacologica Sinica

影响因子:2.912

发表时间:2015

 

摘要:

Aim: To character the specific metabolomics profiles in the sera of Chinese patients with mild persistent asthma and to explore potential metabolic biomarkers.

Methods: Seventeen Chinese patients with mild persistent asthma and age- and sex-matched healthy controls were enrolled. Serum samples were collected, and serum metabolites were analyzed using GC-MS coupled with a series of multivariate statistical analyses.

Results: Clear intergroup separations existed between the asthmatic patients and control subjects. A list of differential metabolites and several top altered metabolic pathways were identified. The levels of succinate (an intermediate in tricarboxylic acid cycle) and inosine were highly upregulated in the asthmatic patients, suggesting a greater effort to breathe during exacerbation and hypoxic stress due to asthma. Other differential metabolites, such as 3,4-dihydroxybenzoic acid and phenylalanine, were also identified. Furthermore, the differential metabolites possessed higher values of area under the ROC curve (AUC), suggesting an excellent clinical ability for the prediction of asthma.

Conclusion: Metabolic activity is significantly altered in the sera of Chinese patients with mild persistent asthma. The data might be helpful for identifying novel biomarkers and therapeutic targets for asthma.

 

Keywords: mild persistent asthma; Chinese patients; serum metabolites; metabolomics; succinate; inosine; GC-MS

 

一、研究背景:

哮喘常由呼吸道炎症导致,但目前诊疗中还缺乏简便易行的呼吸道炎症快速判定措施。来源于尿液、血液和呼出气冷凝液的代谢物可用于疾病的分型和诊断,代谢组学技术通过检测分析上述样本的代谢物指纹图谱可获得与疾病相关的最重要的代谢物和代谢途径。针对这些特异性较强的生物标志物可进一步建立快速检测方法,用于类似哮喘等复杂疾病的分型和早期诊断。本研究尝试通过GC-TOF/MS方法分析哮喘病人血样,从而获得可能用于早期诊断的潜力生物标志物。

 

二、方法流程:




三、研究结果与讨论:

1发现血清代谢组数据在疾病与正常中出现明显区分:

1)使用GC-MS数据可区分轻微持续性哮喘病人和健康人群

2)血清样本代谢组变化证明哮喘可引起人体系统整体代谢变化

 

1 通过多元变量统计分析GC-MS数据建立PCA模型

 

2筛选得到标志性差异物:琥珀酸、二羟基苯甲酸、肌苷

1)TCA循环中仅琥珀酸表现差异:病症可能出于早期,未造成全局变化;

2)许多代谢物与炎症反应、缺氧应激等相关;

3)上述物质可作为哮喘早期诊断生物标志物

 

2 使用VIP筛选标志性差异物,及相关物质的ROC曲线

 

3哮喘发病相关代谢途径研究:

1)影响途径:TCA循环、氮代谢、谷氨酸代谢、核糖代谢、苯丙氨酸代谢

2)TCA循环代谢强化:缺氧导致能量需求旺盛

3)炎症反应相关

4)氮代谢紊乱

 

3 哮喘发病可能涉及的代谢途径

 

四、亮点和展望:

l 发现哮喘病人血清中特异性的代谢物信息;

l 提出哮喘早期诊断可能的标志代谢物;

l 发现与哮喘发病相关的关键代谢途径:

A、增加病例并对代谢物信息进一步解读有助于了解轻微持续性哮喘的发病原因

B、生物标志物的最终认定需在人群队列实验中进行证明

 

阅读文献下载地址:

Chun CHANG, et al, Investigation of metabolic alterations in asthma by GC-MS based metabolomics analysis. Acta Pharmacologica Sinica. 2015. 36:1356-1366.