HILIC-MS/MS for the Determination of Methylated Adenine Nucleosides in Human Urine.
HILIC-MS/MS for the Determination of Methylated Adenine Nucleosides in Human Urine.
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DOI：
10.1021/acs.analchem.1c03829
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发表时间：
2021-12-28
影响因子：
7.4
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Guo C;Hu Y;Cao X;Wang Y
n6 -甲基-2′-脱氧腺苷（m6dA）是新发现的哺乳动物DNA表观遗传标记。N6-甲基腺苷（m6A）、2′- o -甲基腺苷（Am）、n6,2′- o -二甲基腺苷（m6Am）和N6，N6-二甲基腺苷（m62A）是常见的RNA修饰。先前的研究表明，这些甲基化腺苷在核酸中的畸变与癌症之间存在关联。在此，我们建立了Fe3O4/石墨烯基磁分散固相萃取富集和亲水相互作用液相色谱-质谱（HILIC-MS/MS）用于测定人尿样品中的m6dA、m6A、Am、m6Am和m62A。我们发现苹果酸可以改善这些修饰核苷的hilic分离，并显著提高其MS检测的灵敏度。通过这种方法，我们准确地定量了胃癌和结直肠癌患者以及健康对照者尿液样本中这些修饰的腺嘌呤核苷的含量。我们发现，与健康对照相比，胃癌和结直肠癌患者尿中m6dA和Am水平明显较低；胃癌患者尿中m6A水平也较低，而结直肠癌患者则相反。我们共同开发了一种强大的分析方法，用于同时测量人类尿液中五种甲基化腺嘌呤核苷，我们的结果揭示了尿甲基化腺嘌呤核苷水平与胃癌和结直肠癌发生之间的关联，这表明这些修饰的核苷作为早期检测这些癌症的生物标志物的潜在应用。
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.
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影响因子：
64.5
作者：
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影响因子：
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影响因子：
13.6
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影响因子：
25
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影响因子：
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作者：
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