Graphene as adsorbent for highly efficient extraction of modified nucleosides in urine prior to liquid chromatography-tandem mass spectrometry analysis  

作　　者：Cheng Guo Xiaoxiao Zhang Xiujuan Hong Yiqiu Hu Lingna Mao Kezhi Jiang 

机构地区：[1]Cancer Institute(Key Laboratory of Cancer Prevention and Intervention,China National Ministry of Education),The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China [2]Cancer Center,Zhejiang University,Hangzhou 310058,China [3]Key Laboratory of Organosilicon Chemistry and Material Technology,College of Material Chemistry and Chemical Engineering,Hangzhou Normal University,Hangzhou 311121,China [4]Department of General Practice,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China

出　　处：《Chinese Chemical Letters》2024年第4期490-495,共6页中国化学快报（英文版）

基　　金：financially supported by National Natural Science Foundation of China (No.22176167);Fundamental Research Funds for the Central Universities (No.226-2023-00088);Key R&D Program of Zhejiang Province (No.2021C03125)。

摘　　要：RNA modifications have been involved in numerous biological processes, and aberrations of these modifications are tightly associated with various diseases including cancer. Herein, we developed graphenebased solid-phase extraction and robust ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) combined with stable isotope-dilution for simultaneous enrichment and accurate determination of 17 modified nucleosides in human urine. We found graphene could effectively adsorb various modified nucleosides in human urine samples. With this method, we identified and quantified these modified nucleosides in urine samples collected from lung cancer patients and healthy controls.We revealed that the levels of 12 modified nucleosides were all diminished in urine from lung cancer patients, compared with healthy controls. It is worth noting that we demonstrated, for the first time, the presence of 5,2-O-dimethyluridine(m~5U_m) in human urine. Together, we established a robust analytical method for simultaneous determinations of 17 modified nucleosides in human urine, and our results revealed a close correlation between the concentrations of urinary modified nucleosides and the occurrence of lung cancer, implying the potential applications of these modified nucleosides as noninvasive biomarkers for the early detection of lung cancer. Moreover, this study will stimulate future investigations on the regulatory roles of RNA modifications in the initiation and progression of lung cancer.

关 键 词：Mass spectrometry RNA modification Modified nucleosides GRAPHENE BIOMARKER URINE 

分 类 号：O657.63[理学—分析化学] TQ424[理学—化学] R734.2[化学工程]