hydrophilicinteractionliquidchromatographycoupledwithmassspectrometryforserummetabolomicsanalysisofbladdercancer

Bladder cancer (BC) is a fatal malignancy with considerable mortality, and can cause a serious threat to human health. The successful treatment of bladder cancer relies mainly on early detection. Biomarkers are vital to early diagnosis of bladder cancer, and metabonomics play an important role in biomarkers finding. In this study, we used 69 polar metabolites to select the appropriate separation system and develop the zwitterionic hydrophilic chromatography/mass spectrometry (ZIC-HILIC/MS) method. In this method, 50 representative compounds had broad linear ranges between 2-6 orders of magnitude. Moreover the limit of detection of the method was below ng/mL levels. The analysis for six serum samples prepared in parallel showed that this method had good reproducibility, and the RSDs of more than 85% metabolites were less than 30%. Based on this method, it was found that 35 metabolites had significant differences in BC group and healthy control. After screening and validation, the combination of chenodeoxycholic acid, eicosenoic acid, GPC, dodecenoic acid and cystine was a potential biomarker to distinguish BC and normal group. These results indicated that the ZIC. HILIC/MS method could detect diverse metabolites for metabolomic analysis purpose with good reproducibility and stability