Metabolomic profiling of human bladder tissue extracts

Abstract

Introduction: Bladder cancer is a common malignancy affecting the urinary tract and effective biomarkers and for which monitoring therapeutic interventions have yet to be identified.

Objectives: Major aim of this work was to perform metabolomic profiling of human bladder cancer and adjacent normal tissue and to evaluate cancer biomarkers.

Methods: This study utilized nuclear magnetic resonance (NMR) and high-resolution nanoparticle-based laser desorption/ionization mass spectrometry (LDI-MS) methods to investigate polar metabolite profiles in tissue samples from 99 bladder cancer patients.

Results: Through NMR spectroscopy, six tissue metabolites were identified and quantified as potential indicators of bladder cancer, while LDI-MS allowed detection of 34 compounds which distinguished cancer tissue samples from adjacent normal tissue. Thirteen characteristic tissue metabolites were also found to differentiate bladder cancer tumor grades and thirteen metabolites were correlated with tumor stages. Receiver-operating characteristics analysis showed high predictive power for all three types of metabolomics data, with area under the curve (AUC) values greater than 0.853.

Conclusion: To date, this is the first study in which bladder human normal tissues adjacent to cancerous tissues are analyzed using both NMR and MS method. These findings suggest that the metabolite markers identified in this study may be useful for the detection and monitoring of bladder cancer stages and grades.

Keywords: Biomarker; Bladder cancer; Human tissue; Laser mass spectrometry; Metabolomics; NMR.