Proteomics in the dermatology of the future – inclusion of the skin proteome in clinical research and practice / Bjørn

Proteomics in the dermatology of the future – inclusion of the skin proteome in clinical research and practice

This article reviews current and future perspectives on the use of proteomics in a dermatological context. Proteomics refers to studies of the presence and physiological significance of proteins. This article focuses on mass spectrometry as an analysis method with great potential in both research and clinical practice.

BJØRN KROMANN HANSEN is a doctor and Ph.D. student at the Department of Allergy, Skin, and Venereal Diseases at Herlev and Gentofte Hospital. Bjørn’s research focuses on mapping characteristic protein compositions in inflammatory skin diseases, with a primary focus on psoriasis. BEATRICE DYRING-ANDERSEN is a doctor and Ph.D. in dermatology. In addition, she is an associate professor at the Novo Nordisk Foundation Center for Protein Research. She is a group leader and researcher in molecular protein signatures for inflammatory skin diseases, melanoma, and fungal infections.

Medical diagnosis and treatment have traditionally been based on a combination of the patient’s medical history and objective findings. In recent decades, biotechnological breakthroughs have opened the door to individualized medical treatments tailored to the physiology of each individual.

Developments in gene sequencing have made it possible to involve the genome both diagnostically and therapeutically; the genome is a stable foundation for an individual’s physiology and thus phenotypic expression. Because proteins are end-products of the genome and perform all enzymatic processes, the proteome is an important part of the dynamic foundation of a phenotype. Thus, a complete overview of the proteins will be necessary to obtain a full understanding of the physiology.

An independent field of research called proteomics covers several interrelated areas, including studies of the total protein composition, the structure, function, and interactions of the proteins. There are several methods to study the composition of proteins in biological material. Liquid chromatography-tandem mass spectrometry (LC-MS / MS) is frequently used today because it is superior to other technologies in identifying and at the same time quantifying as many proteins as possible in a single sample.2,3 This article focuses on this method and its application in the dermatological context.

The future of mass spectrometry research

Until now, immunohistochemical and antibody-based methods have been preferred for identifying and quantifying proteins in clinical practice and research. Although these methods are reliable and validated, they have certain limitations. The most important of these is that the methods only allow examination of relatively few selected proteins at a time.

With mass spectrometry, it is currently possible to identify thousands of proteins and their relative abundance in a single biological sample. The technology is constantly being improved. An important part of the development of this technology is due to vastly expanded computer power, as large amounts of data are generated. The rapid development in the field has already resulted in several clinical applications in microbiology, screening of newborns for congenital diseases, and urinary toxicology studies.4

In the future, mass spectrometric protein research is expected to enable further findings of biomarkers of importance for diagnosis, prognosis, or treatment response. Furthermore, there is potential to identify the presence of pathological proteins that new drug candidates could target. LC-MS / MS is used in studies for protein analysis of human skin.

Histology and immunohistochemical staining are also used for proteins and other components as part of the diagnostic process in dermatology. Compared to modern proteomics, however, it must be noted that only a limited sample of the total protein composition can be examined with these methods.

CONCLUSION: Mass spectrometric protein studies have already contributed to an increased understanding of physiological and pathological changes in the protein composition of the skin. The technology is becoming further accessible and is expected in the future to increasingly support clinical practice and research.

Conversely, thousands of proteins can be identified and quantified in the skin via mass spectrometry.

In this connection, it is relevant to first know the proteome in healthy skin. In our research group, we have used surplus skin from plastic surgery to characterize the proteome in four separate skin layers and four different cell types that occur in the skin. In total, we have identified 10,700 different proteins, which is the largest number of proteins found in healthy skin in a single study. Several unknown proteins and proteins that have not previously been associated with the skin were found.5 Data from this study are publicly available at https://skin.science/.

Using proteomics, significant findings have also been made concerning the pathogenesis, diagnosis and/or prognosis for several skin conditions, including malignant melanoma, chronic hand eczema, psoriasis and atopic dermatitis.1

Challenges and perspectives

Today mass spectromtric protein research is considered to be a fast and robust method for examining protein compositions in very small amounts of tissues or even few cells. However, there are still challenges and areas where the technology can be further developed.

One of the challenges is that a very large amount of data is generated, and this places great demands on computer power. The fact that mass spectrometry is suitable for examining the protein composition in histologically-fixed tissue samples opens the possibility of making analyzes on skin collected in a clinical context or from previous studies.

Figure 1 – Techniques for collecting skin samples

With different techniques, it is possible to select which skin layers are to be examined. Mass spectrometric protein analysis can be performed on whole or selected skin layers. Cell fractions can be isolated via fluorescence cytometry or laser microscopy.

ORIGINAL PUBLICATION: Fredman G, Skov L, Mann M, Dyring-Andersen B. Towards Precision Dermatology: Emerging Role of Proteomic Analysis of the Skin. Dermatology. 2022; 238 (2): 185-194.

References:

1. Fredman G, Skov L, Mann M, Dyring-Andersen B. Towards Precision Dermatology: Emerging Role of Proteomic Analysis of the Skin. Dermatology. 2022;238(2): 185-194. 2. Aebersold R, Mann M. Mass-spectrometric exploration of proteome structure and function. Nature. 2016;537: 347-355. 3. Sinha A, Mann M. A beginner’s guide to mass spectrometry-based proteomics. Biochem (London). 2020;42(5): 64-69. 4. Sabbagh B, Mindt S, Neumaier M, Findeisen P. Clinical applications of MS-based protein quantification. Proteomics Clin Appl. 2016;10: 323-345. 5. Dyring-Andersen B, Løvendorf MB, Coscia F, et al. Spatially and cell-type resolved quantitative proteomic atlas of healthy human skin. Nat Commun. 2020;11(1): 5587.