RUNX2 as a novel biomarker for early identification of patients progressing to advanced-stage mycosis fungoides

Front Oncol. 2024 Oct 7:14:1421443. doi: 10.3389/fonc.2024.1421443. eCollection 2024.

Abstract

Introduction: The majority of patients with mycosis fungoides (MF) have an indolent disease course, but a substantial fraction (20-30%) of patients progress to advanced stages - usually with a grave prognosis. Early differentiation between indolent and aggressive types of MF is important for the choice of treatment regimen and monitoring of the individual patient. Good biomarkers are therefore desired.

Methods: Here, we used spatial transcriptomics on skin samples at time-of-diagnosis to enable prediction of patients who later progressed to advanced stages of MF. Formalin-fixed, paraffin-embedded skin biopsies at time of diagnosis from six patients with MF who progressed to advanced stages of disease within 4 months to 12 years after diagnosis, and nine patients who remained in early-stage disease over 9 to 27 years were analyzed using the GeoMx Digital Spatial Profiler to capture spatially resolved high-plex RNA gene expression data. Five different regions of interest (the epidermis, the basal layer of epidermis, CD4+ T-cells and neighboring cells, and Pautrier's microabscesses) were profiled for further assessment.

Results and discussion: Interestingly, RUNX2, SHMT2, and MCM7 were upregulated in the enriched population of malignant T-cells in Pautrier's microabscesses in patients who later developed advanced stages of disease. Expression of RUNX2, SHMT2 and MCM7 in malignant T-cells was confirmed in a subset of patients in MF skin using scRNA-seq datasets across multiple studies and correlating with stage of disease. Taken together, we provide first evidence that RUNX2 has potential as a biomarker to identify MF patients progressing to advanced stage disease. As RUNX2 has not previously been linked to MF, our data also shows the analytical strength of combining spatial transcriptomics with scRNA-seq analysis.

Keywords: RNA profiling; biomarkers; digital spatial profiling; mycosis fungoides; spatial transcriptomics.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Part of the funding for the present study was provided by a Nordic WTA Grant provided by NanoString to LI. MD was supported by funds designated for DSP by Aage Bangs Fond (Grant number: 900600), TE was supported by funds designated for DSP by Aage Bangs Fond (Grant number: Not specified), Fonden til Lægevidenskabens Fremme (Grant number: 19-L-0131), Danish Psoriasis Association (Grant number: Not specified), Danske Lægers Forsikringsforening (Grant number: Not specified), Lægeforeningen (Grant number: 2019-3780/40), Robert Wehnerts og Kirsten Wehnerts Fond (Grant number: 18978), Carl og Ellen Hertz´ Videnskabslegat (Grant number: 7179-2), and Grosserer L. F. Foghts Fond (Grant number: 20.010). Novo Nordic Foundation Tandem Program (Grant number: NNF210C0066950). The funding bodies did not have any role in the study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the article for publication.