The current status of clinical proteomics and the use of MRM and MRM³ for biomarker validation

Abstract

The transfer of biomarkers from the discovery field to clinical use is still, despite progress, on a road filled with pitfalls. Since the emergence of proteomics, thousands of putative biomarkers have been published, often with overlapping diagnostic capacities. The strengthening of the robustness of discovery technologies, particularly in mass spectrometry, has been followed by intense discussions on establishing well-defined evaluation procedures for the identified targets to ultimately allow the clinical validation and then the clinical use of some of these biomarkers. Some of the obstacles to the evaluation process have been the lack of the availability of quick and easy-to-develop, easy-to-use, robust, specific and sensitive alternative quantitative methods when immunoaffinity-based tests are unavailable. Multiple reaction monitoring (MRM; also called selected reaction monitoring) is currently proving its capabilities as a complementary or alternative technique to ELISA for large biomarker panel evaluation. Here, we present how MRM³ can overcome the lack of specificity and sensitivity often encountered by MRM when tracking minor proteins diluted by complex biological matrices.

Keywords::

• biomarker
• diagnostic
• evaluation
• mass spectrometry
• MRM
• MRM³
• protein quantification
• validation
• verification

Acknowledgements

We are thankful to Carolyn Roitsch for careful reading of the manuscript and to Corinne Plonquet and Nathalie Picot for handling the references.

Financial & competing interests disclosure

Part of the MRM and MRM³ experiments presented have been obtained thanks to a grant from the French Cancer Institute (INCA), in the frame of the PROMIS project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.