| 基于超高效液相色谱－四极杆－静电场轨道阱质谱的结直肠腺瘤患者血清代谢组学研究 |
| 点此下载全文 |
|
| 基金项目:国家自然科学基金项目（81560703）；广西大学高层次人才基金项目（A3370051006）；湖北民族大学博士启动基金项目 |
|
| 中文摘要:采用超高效液相色谱－四极杆－静电场轨道阱质谱结合主成分分析、正交偏最小二乘判别分析对46例结直肠腺瘤患者（年龄57.8 ± 10.7岁）和45例健康人（年龄54.4 ± 8.2岁）的血清样本进行分析，通过变量权重投影分析和火山图筛选结直肠腺瘤患者血清中的代谢标志物，利用受试者工作特征曲线（ROC）验证代谢标志物的诊断能力。结果表明，两组血清的代谢轮廓有显著差异，筛选并鉴定了20个生物标志物，涉及缬氨酸、亮氨酸和异亮氨酸合成，花生四烯酸代谢、α-亚麻酸代谢、亚油酸代谢、氨酰-tRNA合成、鞘脂代谢、甘油磷脂代谢、色氨酸代谢，其生物标志物16-羟基棕榈酸、花生四烯酸、肌酸、缬氨酸、亮氨酸、色氨酸、α-亚麻酸、牛磺鹅脱氧胆酸、LysoPC（20∶3）的ROC曲线面积（AUC）均大于0.90，特异性与灵敏度较高，对于结直肠腺瘤筛查具有较高的诊断价值和临床应用潜力。研究结果可为基于代谢组学的结直肠腺瘤筛查提供参考资料。 |
| 中文关键词:结直肠腺瘤 超高效液相色谱－四极杆－静电场轨道阱质谱 代谢组学 血清 生物标志物 |
| |
| Metabolomic Study on Serum of Colorectal Adenoma Patients Based on Ultra-high Performance Liquid Chromatography－ Q Exactive Orbitrap Mass Spectrometry |
|
|
| Abstract:The aim of this paper is to explore the metabolic biomarkers and regulation pathways of colorectal adenoma for better understanding of its pathogenesis．The serum samples of 46 colorectal adenoma patients（age 57.8 ± 10.7） and 45 healthy controls（age 54.4 ± 8.2） were analyzed by ultra-high performance liquid chromatography－Q exactive orbitrap mass spectrometry in an untargeted metabolomic approach. The metabolomics data acquired were analyzed using an unsupervised principal component analysis to visualize the grouping trends and detect outliers．A supervised orthogonal partial least squares discriminant analysis（OPLS－DA） was subsequently utilized to maximize the discrimination．The established OPLS－DA model was validated by permutation test for 200 times．Values of variable importance for projection（VIP） were obtained from the OPLS－DA model．Volcano plots of all metabolites were constructed based on the log2-transformed fold-change and log10-transformed?p-value．Then，the most altered serum metabolites responsible for the discrimination between two groups were screened based on the values of variable importance for projection（VIP?> 1.50） and volcano plot analysis（p?< 0.05 with fold change > 1.50 or fold change < 0.67），and further identified using the mzCloud and HMDB databases．The changed metabolic pathways were analyzed using MetaboAnalyst．ROC curves were used to verify the diagnostic ability of those metabolic biomarkers．The results showed that there were significant differences between the serum metabolic profiles of two groups．20 metabolic biomarkers were screened and identified，including essential amino acids，unsaturated fatty acids，sphingolipids，phospholipids and bile acids，and the corresponding disturbed metabolic pathways were valine，leucine and isoleucine biosynthesis，arachidonic acid metabolism，α-linolenic acid metabolism，linoleic acid metabolism，aminoacyl-tRNA biosynthesis，sphingolipid metabolism，glycerophospholipid metabolism and tryptophan metabolism．Among the 20 metabolic biomarkers，juniperic acid，arachidonic acid，creatinine，valine，leucine，tryptophan，linolenic acid，taurochodeoxycholic acid and LysoPC（20∶3） showed high specificity and sensitivity with their areas under the ROC curves（AUC）greater than 0.90，which meant strong diagnostic ability and potential clinical application in serum-based metabolomics screening for colorectal adenoma．This study provides some basic data that could be used to clarify the metabolic characteristics of colorectal adenoma． |
| Key Words:colorectal adenoma ?ultra-high performance liquid chromatography－Q exactive orbitrap mass spectrometry ?metabolomics ?serum ?biomarkers |
| 引用本文：杨宝，梁运啸，黄宗声，涂星，周昌园，胡泽华，文德鉴，张淇淞.基于超高效液相色谱－四极杆－静电场轨道阱质谱的结直肠腺瘤患者血清代谢组学研究[J].分析测试学报,2022,41(5):668-674. |
| 摘要点击次数: 1051 |
| 全文下载次数: 744 |
| 查看全文 下载PDF阅读器 |
|
|
