Background: Mycosis Fungoides (MF) is clinically and histopathologically difficult to differentiate from common skin dermatoses. Its diagnosis also requires a skin biopsy, which may lead to complications such as pain, bleeding, and scarring. Therefore, the aim of this study was to combine tape stripping with data-independent acquisition mass spectrometry (DIA-MS) proteomics to identify novel biomarkers and disrupted biofunctions that may aid in the diagnosis and better understanding of MF pathogenesis.
Method: Lesional and normal human stratum corneum samples were obtained noninvasively by the application of adhesive tape strips on the skin of 28 MF patients followed by DIA-MS proteomic analysis and bioinformatic analyses using the Ingenuity Pathway Analysis (IPA) bioinformatics platform.
Result: In total, 1303 proteins were identified across the samples. The top-250 most variant proteins efficiently separated the samples based on their clinical diagnosis. Also, 290 proteins were significantly changed in the MF cohort compared to normal skin. Of these, the top differentially abundant proteins (GSDMC, PDIA4 and ERP29) were identified as novel biomarkers. IPA analysis predicted the significant inhibition of cell death, and significant activation of immune biofunctions including T-lymphocytes, antigen-presenting cells and recruitment of mononuclear leukocytes in MF lesions. In addition, MF lesions were associated with novel upstream regulators relating to oncogenic processes and immune dysfunction.
Conclusion: The application of tape-stripped sample collection together with the DIA-MS technique could transform the diagnosis of MF by reducing the need for traditional invasive biopsy. Additionally, disrupted biofunctions and upstream regulators identified may serve as useful biomarkers to predict MF progression.