HILIC-MS/MS for the Determination of Methylated Adenine Nucleosides in Human Urine

Overview

Journal Anal Chem

Specialty Chemistry

Date 2021 Dec 13

PMID 34902250

Citations 7

Authors

Cheng Guo

Yiqiu Hu

Xiaoji Cao

Yinsheng Wang

Affiliations

Soon will be listed here.

Abstract

-methyl-2'-deoxyadenosine (mdA) is a newly discovered DNA epigenetic mark in mammals. -methyladenosine (mA), 2'--methyladenosine (A), ,2'--dimethyladenosine (mA), and ,-dimethyladenosine (mA) are common RNA modifications. Previous studies illustrated the associations between the aberrations of these methylated adenosines in nucleic acids and cancer. Herein, we developed FeO/graphene-based magnetic dispersive solid-phase extraction for the enrichment and hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS/MS) for the measurements of mdA, mA, A, mA, and mA in human urine samples. We found that malic acid could improve the HILIC-based separation of these modified nucleosides and markedly enhance the sensitivity of their MS detection. With this method, we accurately quantified the contents of these modified adenine nucleosides in urine samples collected from gastric and colorectal cancer patients as well as healthy controls. We found that, relative to healthy controls, urinary mdA and A levels are significantly lower for gastric and colorectal cancer patients; while gastric cancer patients also exhibited lower levels of urinary mA, the trend was opposite for colorectal cancer patients. Together, we developed a robust analytical method for simultaneous measurements of five methylated adenine nucleosides in human urine, and our results revealed an association between the levels of urinary methylated adenine nucleosides and the occurrence of gastric as well as colorectal cancers, suggesting the potential applications of these modified nucleosides as biomarkers for the early detection of these cancers.

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