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Abstract
Globally, colorectal cancer (CRC) is the third most common malignant neoplasm. However, highly sensitive, specific, noninvasive tests that allow CRC diagnosis at an early stage are still needed. As circulatory blood reflects the physiological status of an individual and/or the disease status for several disorders, efforts have been undertaken to identify candidate diagnostic CRC markers in plasma and serum. In this review, the challenges, bottlenecks and promising properties of mass spectrometry (MS)-based proteomics in blood are discussed. More specifically, important aspects in clinical design, sample retrieval, sample preparation, and MS analysis are presented. The recent developments in targeted MS approaches in plasma or serum are highlighted as well.
Acknowledgements
This work was supported by the Institute for Promotion of Innovation through Science and Technology in Flanders (IWT, IM110568)), an Emmanuel Van der Schueren grant of Vlaamse Liga tegen kanker (VLK), the Flemish Institute for Technological Research (VITO) and the Industrial Research Fund (KU Leuven).
Financial & competing interests disclosure
The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
Colorectal cancer (CRC) is the third most common malignant neoplasm, and it is the third leading cause of cancer-related deaths.
In the near future, early diagnosis of CRC, which currently is the pitfall, will pave the way to a better treatment and higher remission rates provided that easy, fast, and reliable tests are available.
In the search for new noninvasive methods to screen populations for early onset of CRC, discovery and targeted oncoproteomics strategies using blood serum or plasma is plausible as quantifying specific blood components is a widely accepted strategy to assist in diagnosing or ruling out certain disorders.
Typical challenges when performing serum and plasma proteomics are the large dynamic range of proteins in blood, the complex protein content, the biological variation in the human population, and the unintentional potential bias introduced during the blood sampling process.
Comparison of the results of blood proteomics reports is difficult. Therefore, we plead for the use of standards for reporting.
Much is expected from targeted MS approaches in the generation of CRC subtype-specific fingerprints and marker panels for diagnosis as these enable multiplexing and simultaneous quantitation of several features.
We expect that the rapid progress in MS instrumentation development combined with clever bioinformatic solutions will put targeted proteomics approaches in the spotlight for the quantitative analysis of proteins with clinical potential.