Abstract
RNA modifications have been involved in numerous biological processes,and aberrations of these mod-ifications are tightly associated with various diseases including cancer.Herein,we developed graphene-based solid-phase extraction and robust ultra performance liquid chromatography-tandem mass spec-trometry(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(m5Um)in human urine.Together,we established a robust analytical method for simultaneous determinations of 17 modified nucleosides in human urine,and our results re-vealed 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 biomark-ers 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.
基金项目
国家自然科学基金(22176167)
中央高校基本科研业务费专项(226-2023-00088)
浙江省重点研发计划(2021C03125)
NETL
NSTL
万方数据