Protein species as diagnostic markers
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Published on: September 20, 2016
Pascal Steffen1, Marcel Kwiatkowski1, Wesley D Robertson2
1University Medical Centre Hamburg-Eppendorf, Institute for Clinical Chemistry, Department for Mass Spectrometric Proteomics, Martinistraße 52, 20246 Hamburg, Germany.
Insights
Protein species alterations are linked to diseases, similar to HbA1c in diabetes. Focusing on protein species, not just peptides, is crucial for developing new diagnostic markers.
Area of Science:
- Biochemistry
- Proteomics
- Clinical Chemistry
Background:
- Protein species perturbations are associated with various diseases.
- Hemoglobin (HbA1c) is a key diagnostic marker for diabetes, reflecting blood glucose levels.
- Current clinical diagnostics underutilize protein species as markers despite their potential.
Purpose of the Study:
- To review the biochemical characteristics of protein species relevant to disease.
- To explore pathophysiological mechanisms causing protein species modifications.
- To emphasize the importance of screening for protein species markers.
Main Methods:
- Review of biochemical and pathophysiological mechanisms.
- Highlighting techniques for investigating protein species markers in clinical research.
Main Results:
- Protein species can serve as valuable diagnostic markers mirroring pathophysiological events.
- Shifts in protein species levels are linked to disease states.
- Existing clinical proteomics often focuses on peptides, hindering discrimination between healthy and pathologic proteins.
Conclusions:
- The low success rate of FDA-approved protein markers may stem from a gene-centric, peptide-focused approach.
- Screening for disease markers at the protein species level is essential.
- This review provides an overview of relevant techniques for protein species analysis.
Abstract:
Many diseases are associated with protein species perturbations. A prominent example of an established diagnostic marker is the glycated protein species of hemoglobin, termed HbA1c. HbA1c concentration is increased in the blood of diabetes mellitus patients due to their poor control of blood glucose levels resulting in an increased non-enzymatic glycosylation of hemoglobin producing HbA1c. This important diagnostic marker is routinely measured in the blood of diabetes patients. As in the case of HbA1c, protein species can mirror pathophysiological events. Shifts in the levels of protein species can be associated with or even be responsible for disease making them well suited as diagnostic markers. However, only a few protein species are currently used as diagnostic markers in routine clinical chemistry laboratories, despite being widely established in clinical proteomics research. This review provides an overview of the biochemical characteristics associated with protein species as well as examples of pathophysiological mechanisms, which cause modifications in the protein species composition, thereby emphasizing the importance of screening for protein markers at the species level. Further, we highlight techniques, which are currently utilized for investigating protein species markers in clinical research.
Biological Significance:
The success rate of FDA approved diagnostic protein markers until today is very low compared to the number of published candidate disease markers. It is hypothesized that one important reason is the gene-centric view which is still followed in clinical proteomics: In many investigations proteins are still digested in small peptides thus making it nearly impossible to discriminate between healthy proteins and pathologic proteins causing diseases. Thus this review is focusing on the biochemistry and patho-biochemistry of proteins, is highlighting the need for screening for disease markers on the protein species level and is giving an overview about available techniques.
