AI Article Synopsis

  • Early mycosis fungoides (MF) can be challenging to distinguish from psoriasis and chronic spongiotic dermatitis, prompting research into diagnostic markers.
  • The study involved analyzing T cells in skin samples using single-cell transcriptomics, finding 41 differentially expressed genes (DEGs) linked to T-cell receptor (TCR) signaling and apoptosis regulation specifically in MF.
  • GNLY and FYB1 emerged as potential diagnostic biomarkers, showing promising sensitivity and specificity in differentiating MF from the other conditions, with GNLY having an AUC of 0.86 and FYB1 0.79.

Article Abstract

Early mycosis fungoides (MF) and inflammatory dermatoses including psoriasis and chronic spongiotic dermatitis are often difficult to differentiate. We explored diagnostic markers differentiating MF from psoriasis and chronic spongiotic dermatitis via spatially resolved single-cell transcriptome analysis. Single-cell transcriptomics of intraepidermal T cells of MF patches, psoriasis and chronic spongiotic dermatitis were analyzed using CosMx spatial molecular imager utilizing surface markers, including CD3 and CD4. An immunohistochemical study with potential markers was performed to verify clinical utility. Compared to psoriasis and chronic spongiotic dermatitis, 41 upregulated differentially expressed genes (DEGs) in MF were associated with T-cell receptor (TCR) signaling pathway and apoptosis regulation. Protein-protein interaction network analysis of these DEGs revealed a main cluster associated with TCR signaling. Pathway enrichment analysis showed that apoptosis, Th17 cell differentiation, and TCR signaling pathways were enriched in MF. GNLY and FYB1, DEGs with the highest fold change values, were selected as potential diagnostic biomarkers for MF. For immunohistochemistry, biopsy specimens from 150 patients diagnosed with patch MF with CD4 immunophenotype (n = 56), psoriasis (n = 48), and chronic eczema (n = 46) were included. The sensitivity and specificity of GNLY for distinguishing MF and psoriasis/chronic spongiotic dermatitis were 67.9% and 93.6%, respectively. For FYB1, those values were 73.2% and 69.2%, respectively. The AUC values of GNLY and FYB1 were 0.86 and 0.79, respectively. In conclusion, GNLY and FYB1 can be promising diagnostic biomarkers for differentiating early-stage MF from psoriasis and chronic spongiotic dermatitis.

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http://dx.doi.org/10.1016/j.modpat.2024.100681DOI Listing

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