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Updated: Jul 3, 2026
09:04
Selected Reaction Monitoring Mass Spectrometry for Absolute Protein Quantification
Published on: August 17, 2015
From Method-Defined Signals to Reference Measurement Procedures: Two Decades of Mass Spectrometry-Based ProGRP
Donatella Coradduzza1, Emanuela Azara2, Anna La Salvia3
1Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100Sassari, Italy.
Journal of Proteome Research
|July 2, 2026
Summary
Pro-gastrin-releasing peptide (ProGRP) measurement in cancer is improving with mass spectrometry (MS). MS offers more accurate quantification than immunoassays, addressing challenges in biomarker comparability for neuroendocrine neoplasms.
Area of Science:
- Biomarker Discovery
- Quantitative Proteomics
- Measurement Science
Background:
- Pro-gastrin-releasing peptide (ProGRP) is a key biomarker for small cell lung cancer (SCLC) and neuroendocrine neoplasms (NENs).
- Current immunoassay methods face limitations due to low analyte concentrations, proteoform heterogeneity, and lack of comparability.
- Mass spectrometry (MS) offers a more precise approach for quantifying protein biomarkers, resolving isoforms and proteoforms.
Purpose of the Study:
- To review two decades of MS-based ProGRP quantification as a case study in clinical proteomics and measurement science.
- To highlight the evolution of MS techniques for improved selectivity and metrological robustness.
- To address the fundamental comparability issue between immunoassay and MS-based biomarker measurements.
Main Methods:
- Review of mass spectrometry (MS) workflows for ProGRP quantification over 20 years.
- Examination of advancements from single-quadrupole methods to isotope dilution strategies.
- Analysis of performance gains driven by selectivity engineering and internal standardization.
Main Results:
- MS-based methods have evolved towards greater selectivity and metrological robustness in ProGRP measurement.
- Performance improvements in MS were primarily due to selectivity and standardization, not mass analyzer advancements.
- A fundamental discordance exists between immunoassay and MS measurements, as they quantify different entities.
Conclusions:
- Harmonizing quantitative protein biomarker measurements requires a metrological framework, including defined measurands and reference measurement procedures (RMPs).
- Protein-level isotope dilution MS is crucial for establishing traceability and comparability.
- ProGRP serves as an important model for advancing quantitative protein biomarker analysis in clinical proteomics.
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