Abstract

Recent studies have evaluated proper acquisition and storage procedures for the use of serum or plasma for mass spectrometry (MS)-based proteomics. The present study examines the proteome stability of human cerebrospinal fluid (CSF) over time at 23°C (room temperature) and 4°C using surface-enhanced laser desorption/ionization time-of-flight MS. Data analysis revealed that statistically significant differences in protein profiles are apparent within 4 h at 23°C and between 6 and 8 h at 4°C. Inclusion of protease and phosphatase inhibitor cocktails into the CSF samples failed to significantly reduce proteome alterations over time. We conclude that MS-based proteomic analysis of CSF requires careful assessment of sample collection procedures for rapid and optimal sample acquisition and storage.

Highlights

  • Biomarker discovery is at the forefront of biomedical research, and mass spectrometry (MS)-based clinical proteomics has become a popular method to both streamline drug discovery and provide specific diagnostic biomarkers and surrogate end points for a number of human diseases [1,2,3,4,5,6,7]

  • We first analyzed the surface-enhanced laser desorption/ionization (SELDI)-TOF-MS spectra of human cerebrospinal fluid (CSF) incubated at 23°C between 0 and 24 h

  • We examined and compared the spectral pattern of an identical CSF sample incubated at either 23 or 4°C

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Summary

Introduction

Biomarker discovery is at the forefront of biomedical research, and mass spectrometry (MS)-based clinical proteomics has become a popular method to both streamline drug discovery and provide specific diagnostic biomarkers and surrogate end points for a number of human diseases [1,2,3,4,5,6,7]. Any preanalytical errors or procedural differences between the various participant sites, or even the adoption of uniform but suboptimal, untested platform standardization strategies, will affect the final data analysis and potentially lead to erroneous identification of “artifact” biomarkers [14,15]. It is, crucial to characterize the impact of sample collection, handling, and storage procedure and identify best laboratory practices to reduce experimental variation and enhance quality control, even at the biomarker discovery stage

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