Profiling of Urine Carbonyl Metabolic Fingerprints in Bladder Cancer Based on Ambient Ionization Mass Spectrometry

Abstract

The diagnosis of bladder cancer (BC) is currently based on cystoscopy, which is invasive and expensive. Here, we describe a noninvasive profiling method for carbonyl metabolic fingerprints in BC, which is based on a desorption, separation, and ionization mass spectrometry (DSI-MS) platform with N,N-dimethylethylenediamine (DMED) as a differential labeling reagent. The DSI-MS platform avoids the interferences from intra-and/or intersamples. Additionally, the DMED derivatization increases detection sensitivity and distinguishes carboxyl, aldehyde, and ketone groups in untreated urine samples. Carbonyl metabolic fingerprints of urine from 41 BC patients and 41 controls were portrayed and 9 potential biomarkers were identified. The mechanisms of the regulations of these biomarkers have been tentatively discussed. A logistic regression (LR) machine learning algorithm was applied to discriminate BC from controls, and an accuracy of 85% was achieved. We believe that the method proposed here may pave the way toward the point-of-care diagnosis of BC in a patient-friendly manner.

Screening of hepatocellular carcinoma via machine learning based on atmospheric pressure glow discharge mass spectrometry

“…The simplified method was optimized according to the work of our team. 23 Details of the derivatization protocols are shown in Fig. S3 †.…”

“…More details about the DSI platform and its usage can be found in our previous work. 23 High-resolution MS was performed on an Orbitrap Fusion Lumos Tribrid mass spectrometer (Thermo Scientific, San Jose, CA, US). All the MS systems were operated in the positive ion mode.…”

“…This result was verified by the high-resolution MS analyses (Tables S2 and S3 †). 23 It was interesting that among the compounds identified in the general protocol, the number of small molecules was low while large molecules were numer-ous. We assumed it may be caused by the volatilization of light carbonyl compounds in the evaporation procedure.…”

Rapid detection and classification of hongmu by atmospheric pressure ionization mass spectrometry

“…The chromatographic column has an excellent separation effect and can separate substances of complex systems one by one while the APGD ionization source has no separation effect and substances are detected at the same time. Thus, we further introduced porous sand core filters and a heating platform coupled with APGD-MS, 34 which made it possible to detect a sample in 30 seconds.…”

“…Recently, atmospheric pressure glow discharge mass spectrometry (APGD-MS) has been applied to detect liquid 30 and solid 31 samples directly under ambient conditions. This method has been used for structural characterization of synthetic polymers, 32 differentiation of Chinese liquors 33 and urine metabolic fingerprints in bladder cancer 34 based in our group. Compared with LC-MS and GC-MS, APGD-MS simplified sample pretreatment and reduced the time for analysis of sample, but lacked separation ability due to the APGD ionization source without a chromatographic column.…”