非靶标~1H-NMR尿液代谢组学筛选生物标志物组用于心理亚健康的诊断识别

Discovery of Biomarker Panel for Diagnosis of Psychological Suboptimal Health with Non-target ~1H-NMR Urine Metabolomics

心理亚健康(psychological suboptimal health)临床症状表现多样,且无与其密切相关的具体生化指标,因而心理亚健康的判别和诊断成为目前研究中的重点和难点。本研究旨在发现并评价能够用于临床诊断的尿液生物标志物组,为心理亚健康的临床诊断提供依据。通过纳入符合入组标准的24例心理亚健康及18例健康对照受试者,采集空腹晨尿经预处理后进行核磁共振氢谱法(1H-nuclear magnetic resonance spectroscopy,1H-NMR)测试。采用单变量、多元统计及随机森林算法对数据运算分析,以筛选造成组间差异的主要代谢物,发现脯氨酸、苯丙氨酸、葫芦巴碱、酮戊二酸、丙氨酸、柠檬酸、吲哚硫酸酚、乳酸、肌酸、牛磺酸及丙三醇11种代谢物的组间浓度表现出显著性差异(P<0.05,0.01),提示可作为候选诊断生物标志物。进一步结合受试者工作曲线(receiver operating characteristic curve,ROC)及曲线下面积(area under the curve,AUC)对其作为诊断生物标志物组的能力进行评价。结果显示,单一生物标志物对心理亚健康的诊断能力较低,而将柠檬酸、葫芦巴碱及丙三醇3种物质联合应用后诊断能力明显提升(AUC=0.8)。上述结果提示,柠檬酸、葫芦巴碱及丙三醇3种候选生物标志物,可作为生物标志物组用于心理亚健康的诊断。生物标志物组的发现及其应用对于提高心理亚健康诊断与识别的准确度具有重要意义。

The clinical symptoms of psychological suboptimal health are diverse and no specific biochemical indicators is closely related to the state. Therefore, identification and diagnosis of psychological suboptimal health has become a hot topic among the current research. The aim of this study is to detect and evaluate the urine biomarkers that may be used for clinical diagnosis,and to provide evidence for the clinical diagnosis of psychological suboptimal health. A total of 24 patients withpsychological suboptimal health and 18 healthy controls were enrolled in the study. Morning urine after fasting was collected and tested by ~1H-NMR Magnetic Resonance Spectroscopy（~1H-NMR） after pretreatment. Univariate,multivariate and random forest algorithms were used to screen the major metabolites that resulted in differences between groups. The results showed that the concentrations of 11 metabolites containing proline,phenylalanine,trigonelline,2-oxoglutarate,alanine,citrate,indoxylsulfate,lactate,creatine,taurine and glycerol were significantly different（ P 0. 05,0. 01）,suggesting that they could be used as candidate biomarkers for diagnosis. The receiver operating characteristic curve（ ROC） and area under the curve（ AUC） were combined for evaluating the ability of the biomarkers as diagnostic biomarker panels. The results showed that single biomarker had lower diagnostic ability for psychological suboptimal health,and the ability of combination of citric acid,trigonelline and glycerol were significantly improved（ AUC = 0. 8）. Our results suggest that 3 substances of citric acid,trigonelline and glycerol are finally determined as a biomarker panel for psychological suboptimal health diagnosis, biomarker group discovery and application for improving the psychological sub-health diagnosis. The discovery and application of biomarker panel is of great significance to improve the accuracy of psychological suboptimal health diagnosis and identification.