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The development of multiple reaction monitoring assays for liver‐derived plasma proteins
Author(s) -
McKay Matthew J.,
Sherman Jamie,
Laver Matthew T.,
Baker Mark S.,
Clarke Stephen J.,
Molloy Mark P.
Publication year - 2007
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.200700305
Subject(s) - plasma , chemistry , computational biology , chromatography , biology , physics , quantum mechanics
There is wide interpatient variability in toxicity to chemotherapeutic drugs and a lack of routine clinical tests for prospectively identifying patients at risk of developing toxicity from chemotherapy. An empirically driven MS strategy has been developed to monitor liver‐derived plasma proteins as potential biomarkers of early toxicity. Multiple reaction monitoring (MRM) has been used to assess 46 candidate peptides from 18 liver‐derived proteins. Following an iterative process of assay design, optimisation and assessment we selected 29 MRM assays (median CV 4.6%, range 1.2–11.6%) and monitored changes in levels of plasma proteins from a small number of colorectal cancer (CRC) patients undergoing chemotherapy. We demonstrated MRM assay robustness, and show that patients undergo minor elevation in plasma proteins when profiled on Day 3 of the chemotherapeutic regime. The MRM assays were in general agreement with 2‐D DIGE‐based quantitation from the same patient samples. The data supports the application of MRM‐based methods as facile, highly reproducible, medium‐throughput techniques that warrant expanded investigation for clinical utility in identifying patients at risk of developing chemotoxicity.