Biomarker tests have become an important tool in clinical diagnostics. The PSA test evaluates the risk for cancer, and inflammatory and myocardiac panels save lives when performed fast enough. Still, biomarkers, especially protein biomarkers, are not used to their full potential. While novel approaches employ mass spectrometry instead of immunoassay detection, one bottleneck remains: the need for robust, fast, and efficient sample preparation.
BIOMARKERS – THE FUTURE?
Today, blood panels include tests on the cellular level: hematocrit, cell counts and volumes – and on the molecular level: enzymes, hormones, proteins, ions, lipids. Typically, several tubes of 5–10 ml venous blood are required. Procedures are well established in both large and small laboratories on high-throughput instrumentation with methods that have been in use for decades: photometry, turbidometry, immunoassays. Results that diverge from the norm are analyzed to provide further diagnostics support. So, for example, an elevated white blood cell count can mean several things, from harmless infection to leukemia, in extreme cases. Biomarker panels have been developed in recent years to detect inflammatory diseases, predict the risk of cardiovascular problems, and match cancer treatment to patients’ enzyme activity patterns. Currently, information on biomarkers merely complements blood biochemistry data. But do biomarkers hold the potential to replace blood panels altogether? There may be biomarkers that reveal the same or even more specific information than blood panel parameters, calling us to critically assess the informative value and redundancy of the latter. Could the analysis of biomarkers streamline health and disease monitoring to improve patient care? If so, what would be the prerequisites for such a transition and what would be the impact in the clinic?
THE WHOLE PROTEOME AT A FINGER PRICK
In a recent publication (1), researchers from the Max-Planck-Institute in Martinsried near Munich described a novel method for biomarker detection based on mass spectrometry they called plasma proteome profiling. In a fast, three-hour workflow that uses only a microliter of blood, 45 out of 54 FDA-approved biomarkers classified as act in plasma were detected in a robust and reliable manner. The researchers describe a straightforward sample preparation method which can be automated to run up to several hundred samples per day.
Moving such an optimized, fast, and highly robust protocol to the clinic could significantly improve patient care. Requiring only a finger prick of blood, plasma proteome profiling could easily be performed throughout the patient’s lifetime, from birth to the later years of life. Regular monitoring of biomarker levels would allow to detect dangerous changes — such as those associated with diabetes, Alzheimer’s disease or cancer —at early stages and improve treatment options and prognosis.
How do we enable such a transition? Certainly, for a widespread adoption of MS in the clinic, the entire workflow from sample preparation through LC-MS and data analysis needs to become significantly faster to enable the required throughput. Methods will also need to become more robust to obtain comparable results throughout a patient’s lifetime. What about the biomarkers that should be included in this new profiling panel? What combination maximizes the information delivered to a practitioner within a reasonable timeframe? How do we promote biomarker development to complete this profiling panel?
The potential of protocols like plasma proteome profiling in improving health monitoring is clear. Now we need to determine which steps can transform the potential into reality.
(1) Geyer, P.E., Kulak, N.A., Pichler, G., Holdt, L.M., Teupser, D., Mann, M. (2016) Plasma Proteome Profiling to Assess Human Health and Disease. Cell Systems 2, 185-195. http://pubman.mpdl.mpg.de/pubman/item/escidoc:2352959:3/component/escidoc:2352964/1-s2.0-S2405471216300722-main.pdf