期刊
METABOLITES
卷 12, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/metabo12100973
关键词
HILIC-MS/MS; methylated nucleosides; breast cancer; biomarker; urine
资金
- National Natural Science Foundation of China [22176167]
- Natural Science Foundation of Zhejiang Province [LY19B050007]
RNA methylation plays a vital role in diseases like cancer. Researchers have developed a sensitive method to accurately quantify methylated nucleosides in human urine, revealing an association between the contents of urinary methylated nucleosides and the occurrence of breast cancer.
RNA methylation plays a vital role in the pathogenesis of a variety of diseases including cancer, and aberrant levels of modified nucleosides in RNA were revealed to be related to cancer. Urine is a favored source for biomarker discovery due to the non-invasion to patients. Herein, we developed a sensitive hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) method combined with stable isotope dilution for accurate quantification of methylated nucleosides in human urine. With this method, we successfully quantified ten methylated nucleosides in urine samples collected from healthy controls and breast cancer patients. We found N-6-methyladenosine (m(6)A), 2'-O-methyladenosine (A(m)), N-1-methyladenosine (m(1)A), N-6,2'-O-dimethyladenosine (m(6)A(m)), N-1-methylguanosine (m(1)G), 2'-O-methylguanosine (G(m)), 5-methylcytidine (m(5)C) and 2'-O-methylcytidine (C-m) were all decreased in early-stage breast cancer patients, and a nomogram prediction model was constructed. Locally advanced breast cancer patients exhibited elevated levels of urinary 2'-O-methylated nucleosides in comparison to early-stage breast cancer patients. Together, we developed a robust method for the simultaneous determination of methylated nucleosides in human urine, and the results revealed an association between the contents of urinary methylated nucleosides and the occurrence of breast cancer, which may stimulate future studies about the regulatory roles of these methylated nucleosides in the initiation and progression of breast cancer.
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