Volatile organic compounds analysis optimization and biomarker discovery in urine of Non-Hodgkin lymphoma patients before and during chemotherapy

Abstract

The Non-Hodgkin's lymphoma (NHL) is a severe and common neoplasm generated by metabolic changes due to cells mutations. Its prognostic or diagnosis seems therefore viable by monitoring metabolites produced and secreted into biological fluids or tissues. Hence, we used an untargeted metabolomics approach to evaluate if the profiles of volatile organic compounds (VOCs) present in urine would serve to Non-Hodgkin's lymphoma (NHL) prognostic or diagnostic. Headspace solid-phase microextraction (HS-SPME) was optimized and applied to pools of urine or serum samples from healthy patients after optimization using a Central Composite Design (CCD), followed by gas chromatography coupled to mass spectrometry (GC–MS) analysis. CCD factorial design 23 and the response surfaces indicated the optimized extraction parameters. Individual urine samples from healthy and diseased subjects were prepared and analyzed by the optimized method, and a thorough statistical analysis revealed several metabolites as potential biomarkers for NHL as well as able to describe the patient's metabolic profile before each chemotherapy cycle. This approach seems promising in contributing to the prognosis and choice of appropriate treatment of NHL for each individual.