Identification of biomarkers of mastocytosis: Insights from whole transcriptome analysis with single cell resolution and immunohistochemical analysis

Summary: Systemic mastocytosis (SM) is a rare disorder characterized by an excessive accumulation of mast cells in various tissues, presenting significant challenges in both diagnosis and treatment. In this study, we aimed to identify pathway expression profiles and potential biomarkers in the skin of SM patients. We performed whole transcriptome analysis with single-cell resolution using Visium HD (10x Genomics) on skin samples from two SM patients. This was followed by in-silico analysis of mast cell-specific genes (TPSG1, CMA1, CPA3), which encode mast cell tryptase, chymase, and carboxypeptidase, respectively, as well as activation markers for FcεRI-mediated Ca2+ mobilization and NF-kB pathways, to definitively characterize the mast cell population. Further analysis revealed that members of the galectin family—particularly galectin-3 and galectin-8, glycan-binding proteins involved in immune modulation and inflammation—are expressed by mast cells. Immunohistochemistry (IHC) confirmed the expression of these galectins in mast cells within mastocytoma and cutaneous mastocytosis. In addition, Visium HD and IHC data both showed prominent galectin-3 expression in keratinocytes and galectin-8 expression in endothelial cells. These findings suggest that targeting galectin-3 and galectin-8, which may play a role in disease pathology, could offer a promising approach for developing precision therapies for mastocytosis. Kayla Danesh¹, Ching-Han Tsao¹, Feng-Jen Lin³, Gene Kim^{1, 2}, Hung-Lin Chen⁴, Fu-Tong Liu^{1, 3} 1. Dermatology, University of Southern California Keck School of Medicine, Los Angeles, CA, United States. 2. Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA, United States. 3. Institute of Biomedical Sciences Academia Sinica, Taipei, Taiwan. 4. Clinical Pharmacy, Taipei Medical University College of Pharmacy, Taipei, Taiwan. Bioinformatics, Computational Biology, and Imaging