Proteomic Screening and Verification of Biomarkers in Different Stages of Mycosis Fungoides: A pilot Study

Abstract

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma; in advanced stages, it can involve multiple organs and has a poor prognosis. Early detection of the disease is still urgent, but there is no optimal therapy for advanced MF. In the present study, quantitative proteomic analyses (label-free quantitation, LFQ) were applied to tissue samples of different stages of MF and tissue samples from controls (eczema patients and healthy donors) to conduct preliminary molecular analysis to clarify the pathogenesis of the disease. Differential protein expression analysis demonstrated that 113 and 305 proteins were associated with the early and advanced stages of MF, respectively. Gene ontology (GO) enrichment analysis was conducted to determine the potential functions of the proteins, which could be classified into three categories: biological process, cellular component, and molecular function. The results revealed that a series of biological processes, including “initiation of DNA replication” and “nucleosome assembly,” were involved in the disease. Moreover, cellular components, including the “desmosome” and “integrin complex,” may affect the invasion and metastasis of MF via molecular functions, including “integrin binding” and “cadherin binding”. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis demonstrated that “focal adhesion DNA replication,” “Toll-like receptor signalling pathway” and other pathways were also involved. A parallel reaction monitoring (PRM) assay was applied to validate the identified differentially expressed proteins. In conclusion, the above proteomic findings may have great diagnostic and prognostic value in diverse malignancies, especially MF. Nevertheless, further studies are still needed to explore the precise mechanisms of MF.

Tape stripped stratum corneum samples are suitable for diagnosis and comprehensive proteomic investigation in mycosis fungoides

“…Similarly, the role of other activated molecular pathways, such as Rho [54], NRF2-mediated oxidative stress response in cancer inflammation [55] and E-cadherin for invasion, migration, survival of tumours [56] have been reported in the literature. In a previous proteomic study of MF lesions, 318 proteins were found to be associated with the MF development [4]. In line with the findings from the current study, their subsequent gene ontology enrichment analysis determined that, among others, the significantly changed proteins were likely involved in integrin binding and cadherin binding.…”

“…CD44 has been implicated in the progression of many cancers due to its role in intracellular signalling pathways, which result in cell proliferation, migration, adhesion and invasion [41]. In a proteomic study by Gan et al, this protein was also reported to be significantly increased in patients with advanced-stage MF compared to the early-stage MF [4]. The overexpression of CD44 in MF lesions could be linked to its role in regulating the survival of the Th1 subset of CD4+ T lymphocytes, which supports the Th1 environment reported in the early MF [42,43].…”

“…Gasdermin Previous studies have also used mass spectrometry-based proteomics to differentiate between the blood [30] and biopsy samples [4] obtained from patients with or without MF, identifying potential biomarkers of MF. However, the current study aimed to identify the proteome changes between MF and normal stratum corneum using tape-stripped samples.…”

“…MF is a rare disease, with an annual worldwide incidence of approximately 6−7 cases per million [3]. Although MF follows an indolent course in its early stages, advanced stages may involve multiple organs, resulting in a poor prognosis [4].…”

The Role of Cytokines in Cutaneous T Cell Lymphoma: A Focus on the State of the Art and Possible Therapeutic Targets

“…MF/SS pathogenesis and the mechanisms involved in their progression from early to advanced phases are far from being fully understood [10][11][12]. Different players are involved in MF/SS, such as gene alterations, changes in the microenvironment composition, cytokine balance changes, and transcriptional pathways [10][11][12][13][14][15][16]. All these players are intrinsically linked.…”