Abstract
Colorectal cancer and gastric cancer are the most prevalent gastrointestinal malignancies worldwide, and early detection of these cancers is crucial to reduce their incidence and mortality. RNA methylation plays an important regulatory role in a variety of physiological activities, and it has drawn great attention in recent years. Methylated adenosine (A) modifications such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 2′-O-methyladenosine (Am), N6,2′-O-dimethyladenosine (m6Am), and N6,N6-dimethyladenosine (m62A) are typical epigenetic markers of RNA, and they are closely correlated to various diseases including cancer. Serum is a valuable source of biofluid for biomarker discovery, and determination of these adenosine modifications in human serum is desirable since they are emerging biomarkers for detection of diseases. In this work, a targeted quantitative analysis method using hydrophilic interaction liquid chromatography–tandem mass spectrometry (HILIC-MS/MS) was developed and utilized to analyze these methylated adenosine modifications in serum samples. The concentration differences between the healthy volunteers and cancer patients were evaluated by Mann–Whitney test, and receiver operator characteristic (ROC) curve analysis was performed to access the potential of these nucleosides as biomarkers. We demonstrated the presence of the m6Am in human serum for the first time, and we successfully quantified the concentrations of A, m6A, m1A, and m6Am in serum samples from 99 healthy controls, 51 colorectal cancer patients, and 27 gastric cancer patients. We found that the levels of m6A and m6Am in serum were both increased in colorectal cancer or gastric cancer patients, compared to that in healthy controls. These results indicate that m6A and m6Am in serum may act as potential biomarkers for early detection and prognosis of colorectal cancer and gastric cancer. In addition, the present work will stimulate investigations on the effects of adenosine methylation on the initiation and progression of colorectal cancer and gastric cancer.
Highlights
Colorectal cancer and gastric cancer are two common malignancies that are the second and third causes of cancerrelated deaths all over the world, respectively (Brenner et al, 2014; Siegel et al, 2017; Bray et al, 2018)
HILIC is widely used for the separation of compounds with high polarity, and we found that m1A can be retained well on the HILIC column
By applying the established method, we successfully revealed, for the first time, the presence of m6Am in human serum and quantified the concentrations of A, m6A, m1A, and m6Am in 177 serum samples from three groups, namely, healthy volunteers, colorectal cancer patients, and gastric cancer patients
Summary
Colorectal cancer and gastric cancer are two common malignancies that are the second and third causes of cancerrelated deaths all over the world, respectively (Brenner et al, 2014; Siegel et al, 2017; Bray et al, 2018). The screening and diagnosis of colorectal cancer and gastric cancer mainly depend on results of colonoscopy and gastroscopy, respectively, which are both invasive to patients, leading to low compliance. From this point of view, it is essential to discover novel non-invasive biomarkers for early detection of colorectal cancer and gastric cancer to elongate the survival time and decrease the pains of patients. Methylation modifications in RNA had been identified in the 1970s (Dubin and Taylor, 1975; Perry et al, 1975), understanding of the functions of RNA methylation was limited until the identification of regulatory proteins such as fat mass and obesity-associated protein (FTO) (Jia et al, 2011). It has been revealed that RNA methylation participates in the initiation and progression of a number of diseases including cancer (Fang et al, 2021)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
