Publication

Protein species as diagnostic markers

Steffen, P., Kwiatkowski, M., Robertson, W. D., Zarrine-Afsar, M., Deterra, D., Richter, V. & Schlueter, H., 16-Feb-2016, In : Journal of proteomics. 134, p. 5-18 14 p.

Research output: Contribution to journalReview articleAcademicpeer-review

  • Pascal Steffen
  • Marcel Kwiatkowski
  • Wesley D. Robertson
  • Mash Zarrine-Afsar
  • Diana Deterra
  • Verena Richter
  • Hartmut Schlueter

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. (C) 2015 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)5-18
Number of pages14
JournalJournal of proteomics
Volume134
Publication statusPublished - 16-Feb-2016
Externally publishedYes

    Keywords

  • Mass spectrometry, Protein species, Clinical chemistry, Protein diagnostics, UBIQUITIN-PROTEASOME SYSTEM, TANDEM MASS-SPECTROMETRY, TOP-DOWN PROTEOMICS, PERFORMANCE LIQUID-CHROMATOGRAPHY, LINKED-IMMUNOSORBENT-ASSAY, RESOLVED IMMUNOFLUOROMETRIC ASSAY, HUMAN CHORIONIC-GONADOTROPIN, PROSTATE-SPECIFIC ANTIGEN, HIGH-FIELD ORBITRAP, C-REACTIVE PROTEIN

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