posted on 2021-12-13, 23:14authored byCheng Guo, Yiqiu Hu, Xiaoji Cao, Yinsheng Wang
N6-methyl-2′-deoxyadenosine
(m6dA) is a newly discovered DNA epigenetic mark in mammals. N6-methyladenosine (m6A), 2′-O-methyladenosine (Am), N6,2′-O-dimethyladenosine (m6Am), and N6,N6-dimethyladenosine (m62A) are common
RNA modifications. Previous studies illustrated the associations between
the aberrations of these methylated adenosines in nucleic acids and
cancer. Herein, we developed Fe3O4/graphene-based
magnetic dispersive solid-phase extraction for the enrichment and
hydrophilic interaction liquid chromatography–mass spectrometry
(HILIC-MS/MS) for the measurements of m6dA, m6A, Am, m6Am, and m62A 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 m6dA and Am levels are significantly
lower for gastric and colorectal cancer patients; while gastric cancer
patients also exhibited lower levels of urinary m6A, 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.