A distinct glycerophospholipid metabolism signature of acute graft versus host disease with predictive value
A distinct glycerophospholipid metabolism signature of acute graft versus host disease with predictive value
复制标题
急性移植物抗宿主病的独特甘油磷脂代谢特征具有预测价值
DOI：
10.1172/jci.insight.129494
复制
发表时间：
2019-08-22
期刊：
影响因子：
8
通讯作者：
Hu，Xiaoxia
中科院分区：
文献类型：
--
作者：
Liu，Yue;Huang，Aijie;Hu，Xiaoxia
背景：急性移植物抗宿主病（aGvHD）是限制同种异体造血细胞移植（alloHSCT）成功结果的主要因素。目前，很少有经过验证的生物标志物可以在临床环境中帮助预测aGvHD的风险。方法：我们进行了一项综合代谢组学和转录组学研究，并在2个单独的队列中确定了区分患有aGvHD的同种异体造血干细胞移植受体和没有aGvHD的同种异体造血干细胞移植受体的生物标志物。结果对38个显著改变的代谢物和1148个差异表达基因的通路分析揭示了甘油磷脂（GPL）代谢网络的明显改变。随后，我们基于GPL代谢的5种代谢物标记物建立了aGvHD风险评分（GRS），以预测aGvHD的风险。在训练组和验证组中，GRS的阳性预测值分别为92.2%和89.6%。此外，高GRS与较差的总生存率相关。gpl相关脂肪酶的基因表达在aGvHD样品中显著改变，导致gpl失调。结论利用整合的“组学”分析，我们揭示了aGvHD发病机制背后的分子扰动的全面观点。我们的工作代表了对独特的代谢和转录组网络的初步研究，这可能有助于在早期阶段识别aGvHD并促进先发制人的治疗。国家自然科学基金（NSFC; 81530047, 81870143, 81470321, 81770160, 81270567, 81270638, 81573396, 81703674）为材料、加工、代谢组学和转录组学研究提供资金。上海市科委上海扬帆计划项目（17YF1424700）、上海市卫生和计划生育委员会奖学金项目（2017BR012）、上海市健康产业专项临床研究项目（20184Y0054）资助。青年学者资助项目：17YF1424700 （to YL）、2017BR012 （to XH）、20184Y0054 （to QC）。
BACKGROUNDAcute graft versus host disease (aGvHD) is a major factor that limits the successful outcomes of allogeneic hematopoietic cell transplantation (alloHSCT). Currently, there are few validated biomarkers that can help predict the risk of aGvHD in clinical settings.METHODSWe performed an integrated metabolomics and transcriptomics study and identified biomarkers that distinguish alloHSCT recipients with aGvHD from alloHSCT recipients without aGvHD in 2 separate cohorts.RESULTSPathway analysis of 38 significantly altered metabolites and 1,148 differentially expressed genes uncovered a distinctly altered glycerophospholipid (GPL) metabolism network. Subsequently, we developed an aGvHD risk score (GRS) based on 5 metabolite markers from GPL metabolism to predict the risk of aGvHD. GRS showed a positive predictive value of 92.2% and 89.6% in the training and validation cohorts, respectively. In addition, high GRS was correlated with poor overall survival. Gene expressions of GPL-related lipases were significantly altered in aGvHD samples, leading to dysregulated GPLs.CONCLUSIONUsing integrative “Omic” analysis, we unraveled a comprehensive view of the molecular perturbations underlying the pathogenesis of aGvHD. Our work represents an initial investigation of a unique metabolic and transcriptomic network that may help identify aGvHD at an early stage and facilitate preemptive therapy. FUNDING National Natural Science Foundation of China (NSFC; 81530047, 81870143, 81470321, 81770160, 81270567, 81270638, 81573396, 81703674) provided funding for material, processing, metabolomics, and transcriptomics studies. This work was also supported by Shanghai Sailing Program from Science and Technology Commission Shanghai Municipality (17YF1424700), the Scholarship from Shanghai Municipal Health and Family Planning Commission (2017BR012), and the Special Clinical Research in Health Industry in Shanghai (20184Y0054). The projects supporting young scholars are 17YF1424700 (to YL), 2017BR012 (to XH), and 20184Y0054 (to QC).