Zhang Ziyan, Wu Xiaojin, Zhou Meng, Qi Jiaqian, Zhang Rui, Li Xueqian, Wang Chang, Ruan Changgeng, Han Yue
National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Front Pharmacol. 2022 May 24;13:845275. doi: 10.3389/fphar.2022.845275. eCollection 2022.
ITP is a common autoimmune bleeding disorder with elusive pathogenesis. Our study was implemented to profile the plasma metabolic alterations of patients diagnosed with ITP, aiming at exploring the potential novel biomarkers and partial mechanism of ITP. The metabolomic analysis of plasma samples was conducted using GC-MS on 98 ITP patients and 30 healthy controls (HCs). Age and gender matched samples were selected to enter the training set or test set respectively. OPLS-DA, t-test with FDR correction and ROC analyses were employed to screen out and evaluate the differential metabolites. Possible pathways were enriched based on metabolomics pathway analysis (MetPA). A total of 85 metabolites were investigated in our study and 17 differential metabolites with diagnostic potential were identified between ITP patients and HCs. MetPA showed that the metabolic disorders of ITP patients were mainly related to phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and glyoxylate and dicarboxylate metabolism. Additionally, we discriminated 6 differential metabolites and 5 enriched pathways in predicting the resistance to glucocorticoids in chronic ITP patients. The distinct metabolites discovered in our study could become novel biomarkers for the auxiliary diagnosis and prognosis prediction of ITP. Besides, the dysregulated pathways might contribute to the development of ITP.
免疫性血小板减少症(ITP)是一种常见的自身免疫性出血性疾病,其发病机制尚不明确。我们开展这项研究旨在剖析ITP患者血浆代谢变化情况,以探寻ITP潜在的新型生物标志物及部分发病机制。采用气相色谱 - 质谱联用(GC - MS)技术对98例ITP患者和30例健康对照(HCs)的血浆样本进行代谢组学分析。选取年龄和性别匹配的样本分别纳入训练集或测试集。运用正交偏最小二乘法判别分析(OPLS - DA)、经错误发现率(FDR)校正的t检验以及ROC分析来筛选和评估差异代谢物。基于代谢组学通路分析(MetPA)对可能的代谢通路进行富集。本研究共检测了85种代谢物,在ITP患者和HCs之间鉴定出17种具有诊断潜力的差异代谢物。MetPA显示,ITP患者的代谢紊乱主要与苯丙氨酸、酪氨酸和色氨酸生物合成、苯丙氨酸代谢以及乙醛酸和二羧酸代谢有关。此外,我们在预测慢性ITP患者对糖皮质激素的耐药性方面鉴别出6种差异代谢物和5条富集通路。我们研究中发现的独特代谢物可能成为ITP辅助诊断和预后预测的新型生物标志物。此外,失调的代谢通路可能与ITP的发生发展有关。