High throughput ion mobility-mass spectrometry metabolomics for prostate cancer detection

XIAOLING ZANG; MARÍA EUGENIA MONGE; DAVID A. GAUL; FACUNDO M. FERNANDEZ

Conferencia; Pittcon 2018; 2018

Current screening approaches for prostate cancer (PCa) include the prostate-specific antigen (PSA) blood test and digital rectal examination. However, the PSA test suffers from over-diagnosis and overtreatment, and digital rectal exams are limited by low detection rates in non-palpable PCa growths. Metabolomics is being increasingly applied to explore disease biomarkers, with mass spectrometry (MS)-based platforms being widely used due their intrinsic sensitivity. The majority of metabolomics studies employ chromatography or capillary electrophoresis prior to MS analysis, which are relatively time consuming. Here, we show the high-throughput metabolic profiling of serum samples from PCa patients and healthy subjects using flow injection (FI) electrospray traveling wave ion mobility spectrometry (TWIMS) time-of-flight (ToF) MS. Compared with traditional techniques, the FI-TWIMS-ToF-MS method offers distinct advantages of rapid sample analysis and separation of compounds based on their differences in collision cross section ? compounds with different charge states and classes fall into distinct regions in the m/z vs. drift time plot, facilitating metabolite structural identification with reduced false-positive assignments. In this study, a panel of 10 chemically-identified compounds predicted the presence of PCa in serum samples with 90.2% sensitivity, 83.3% specificity and 87.4% accuracy, using orthogonal partial least squares discriminant analysis, showing the feasibility of detecting PCa by means of high throughput TWIMS-MS.