Deep Visual Proteomics uncovers mycosis fungoides-specific biomarkers

Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, presents challenges, including a lack of tumour cell-specific diagnostic markers and a lack of potential treatment targets. Deep Visual Proteomics (DVP) was found to effectively address these challenges. Potential diagnostic and prognostic markers were identified, as well as potential treatment targets.

A Danish group developed DVP, incorporating high-resolution staining and imaging on FFPE sections, AI-driven single-cell phenotyping, automated single-cell laser microdissection, and ultrasensitive mass spectrometry (MS) [1]. The DVP workflow consisted of section preparation, staining and imaging, and imaging analysis; followed by feature extraction and classification. The third step was laser microdissection and the fourth and final was mass spectrometry and data analysis, for unbiased MS-based proteomics to differentiate reactive and malignant T cells.

This resulted in the identification of approximately 5000 protein groups from a cellular volume of 175,000 μm³, equivalent to 400 single cells. Potential early diagnostic markers, like Mini-Chromosome Maintenance proteins, were found. Longitudinal proteome analysis of early- and advanced-stage MF revealed significant upregulation of proteins in advanced MF stages, including those involved in cell-cell adhesion, cytoskeleton organisation, protein folding, and VEGFA-VEGFR2 and PI3K-Akt-mTOR signal transduction (suggesting angiogenic factors promoting T cell migration to the epidermis). These findings provide insights into the mechanisms underlying the epidermotropism of malignant T-cells in MF. The results point towards potential therapeutic targets, such as inhibitors of EGFR and VEGF.

To follow-up on these findings, the Danish researchers aim to integrate multiplex imaging-powered DVP and transcriptomics to gain deeper insights into the tumour microenvironment dynamics of MF.

1. Zheng X, et al. Deciphering reliable mycosis fungoides-specific diagnostic classifiers and personalized therapeutic regimens through spatial single-cell type proteomics in tissues. Abstract A-192, EORTC-CLTG 2024, 9-11 October 2024, Lausanne, Switserland.

Posted on 14 October 202414 October 2024