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The development of multiple reaction monitoring assays for liver-derived plasma proteins. | LitMetric

The development of multiple reaction monitoring assays for liver-derived plasma proteins.

Proteomics Clin Appl

Australian Proteome Analysis Facility Ltd (APAF), Macquarie University, Sydney, Australia; Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, Australia.

Published: December 2007

AI Article Synopsis

  • There is considerable variation among patients in how they react to chemotherapy, and current clinical tests do not effectively identify those at risk of experiencing toxicity.* -
  • A new monitoring strategy using mass spectrometry (MS) focuses on liver-derived plasma proteins as potential early indicators of chemotherapy toxicity, assessing 46 candidate peptides from 18 proteins.* -
  • The study successfully developed and validated 29 multiple reaction monitoring (MRM) assays, showing that patients experienced minor increases in certain plasma proteins by Day 3 of treatment, indicating the MRM approach could help identify patients at risk for chemotoxicity.*

Article Abstract

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.

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Source
http://dx.doi.org/10.1002/prca.200700305DOI Listing

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