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Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
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Absolute Quantification of Pan-Cancer Plasma Proteomes Reveals Unique Signature in Multiple Myeloma
David Kotol1,2, Jakob Woessmann1,2, Andreas Hober1,2
1Science For Life Laboratory, KTH Royal Institute of Technology, 114 28 Stockholm, Sweden.
Cancers
|October 14, 2023
Summary
Data-independent acquisition mass spectrometry enabled precise protein quantification in 1800 plasma samples. A seven-protein panel shows promise for diagnosing multiple myeloma with high accuracy.
Area of Science:
- Proteomics
- Mass Spectrometry
- Biomarker Discovery
Background:
- Data-independent acquisition (DIA) mass spectrometry is a powerful quantitative tool with applications in precision medicine.
- Stable isotope recombinant protein standards enhance protein identification and absolute quantification accuracy.
Purpose of the Study:
- To profile a pan-cancer cohort of 1800 blood plasma samples from 15 cancer types using targeted proteomics.
- To identify and validate a protein biomarker panel for multiple myeloma diagnosis.
Main Methods:
- Utilized a comprehensive targeted proteomics approach with DIA mass spectrometry.
- Performed absolute quantification of 253 proteins in multiplex across 1800 plasma samples.
- Applied differential expression analysis and machine learning for biomarker identification.
Main Results:
- Achieved low intra-assay variability (CV = 17.2%) for 1013 quantified peptides.
- Identified a seven-protein biomarker panel for multiple myeloma diagnosis.
- Developed a prediction model with an AUC of 0.96 for multiple myeloma detection.
Conclusions:
- The developed targeted proteomics assay is robust and reproducible for large-scale plasma profiling.
- The identified seven-protein panel, including complement C1 complex, JCHAIN, and CD5L, shows significant potential for early multiple myeloma diagnosis.
- These proteins, known to interact with immunoglobulins, offer insights into multiple myeloma pathogenesis.

