LC‐MS‐based serum metabolic profiling for genitourinary cancer classification and cancer type‐specific biomarker discovery

Abstract

Bladder cancer (BC) and kidney cancer (KC) are the first two commonly occurring genitourinary cancers in China. In this study, a comprehensive LC-MS-based method, which utilizes both reversed phase liquid chromatography (RPLC) and hydrophilic interaction chromatography (HILIC) separations, has been carried out in conjunction with multivariate data analysis to discriminate the global serum profiles of BC, KC, and noncancer controls. An independent test set consisting of different patients has been used to objectively evaluate the predictive ability of the analysis platform. Excellent sensitivity and specificity have been achieved in detection of KC and BC. The results suggest that serum metabolic profiling could be used for different types of genitourinary cancer diagnosis. Furthermore, cancer type-specific biomarkers were found through a critical selection criterion. As a result, eicosatrienol, azaprostanoic acid, docosatrienol, retinol, and 14'-apo-beta-carotenal were found as specific biomarkers for BC; and PE(P-16:0e/0:0), glycerophosphorylcholine, ganglioside GM3 (d18:1/22:1), C17 sphinganine, and SM(d18:0/16:1(9Z)) were found as specific biomarkers for KC. Receiver operating characteristic (ROC) analysis was used for the preliminary evaluation of the biomarkers. These biomarkers have great potential to be used in the clinical diagnosis after further rigorous assessment.

Lipid Metabolism Profiling and Bladder Cancer

“…fact that tumor cells utilize enhanced β-oxidation of fatty acids which are the skeleton of TG for rapid growth. Similar to these results, Lin et al [12] found that patients with bladder cancer have enhanced level of phosphatidylcholine. In another study [13], canine bladder cancer tissue sections and adjacent normal tissues were imaged using desorption electrospray ionization (DESI) mass spectrometry and both glycerophospholipid and sphingolipid profiles between the tissue types differed, both in the intensities of the lipid signals present and the pattern of the lipid signals.…”

Relative quantification of amine-containing metabolites using isobaric N,N-dimethyl leucine (DiLeu) reagents via LC-ESI-MS/MS and CE-ESI-MS/MS

“…Determining the relative abundance of metabolites with MS-based techniques has been successfully applied to discover potential metabolic biomarkers of various human diseases. 21-24 …”

Nanoflow-Nanospray Mass Spectrometry Metabolomics Reveals Disruption of the Urinary Metabolite Profiles of HIV-Positive Patients on Combination Antiretroviral Therapy

“…However, a C17 sphinganine has been detected in human plasma as a biomarker of kidney cancer. 40 The role of sphingolipid bases in HIV infection is currently unknown, but sphingolipids and their metabolites can initiate cellular apoptosis 41 , regulate HIV viral entry into cells 42,43 and are associated with age-related changes in cholesterol/low density lipoprotein levels. 44 Concentrations of a tetrapeptide increased in patients on atazanavir, possibly as a result of TDF and reduced proximal tubular function and reduced re-uptake of low molecular weight proteins.…”