Determination of dimethylated nucleosides in serum from colorectal cancer patients by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

RNA modifications play a crucial regulatory role in a variety of biological processes and are closely related to numerous diseases, including cancer. The diversity of metabolites in serum makes it a favored biofluid for biomarkers discovery. In this work, a robust and accurate hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) approach was established for simultaneous determination of dimethylated nucleosides in human serum. Using the established method, we were able to accurately quantify the concentrations of N-2'-O-dimethyladenosine (mA), N,N-dimethylguanosine (mG), and 5,2'-O-dimethyluridine (mU) in serum samples from 53 healthy controls, 57 advanced colorectal adenoma patients, and 39 colorectal cancer (CRC) patients. The results showed that, compared with healthy controls and advanced colorectal adenoma patients, the concentrations of mA and mG were increased in CRC patients, while the concentration of mU was decreased in CRC patients. These results indicate that these three dimethylated nucleosides could be potential biomarkers for early detection of colorectal cancer. Interestingly, the level of mU was gradually decreased from healthy controls to advanced colorectal adenoma patients to CRC patients, indicating mU could also be used to evaluate the level of malignancy of colorectal tumor. In addition, this study will contribute to the investigation on the regulatory mechanisms of RNA dimethylation in the onset and development of colorectal cancer.