分析化学2025，Vol.53Issue(11)：1848-1859,中插4-中插29,38.DOI:10.19756/j.issn.0253-3820.251200
应用极性扩展液相色谱-质谱系统筛查细胞外囊泡的前列腺癌生物标志物
Polarity-extended Liquid Chromatography-Mass Spectrometry System for Prostate Cancer Biomarker Screening Based on Extracellular Vesicles
摘要
Abstract
Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.关键词
极性扩展液相色谱-质谱联用/代谢组学/脂质组学/细胞外囊泡/前列腺癌Key words
Polarity-extended liquid chromatography-mass spectrometry/Metabolomics/Lipidomics/Extracellular vesicles/Prostate cancer引用本文复制引用
XIAO Lu-Lu,LIU Xue-Song,CHEN Meng-Xuan,PAN Shan-Shan,WANG Yi-Chen,HUANG Tao-Hong,ZHONG Qi-Sheng,CHEN Yong,XU Teng-Fei,ZHAO Jia-Hui..应用极性扩展液相色谱-质谱系统筛查细胞外囊泡的前列腺癌生物标志物[J].分析化学,2025,53(11):1848-1859,中插4-中插29,38.基金项目
浙江省自然科学基金项目(No.TGY23H090038)和国家自然科学基金项目(No.82204584,22304061)资助. Supported by the Zhejiang Provincial Natural Science Foundation(No.TGY23H090038)and the National Natural Science Foundation of China(Nos.82204584,22304061). （No.TGY23H090038）
