Cellular and molecular landscape of primary dermatofibrosarcoma protuberans: Insights from single‐cell RNA sequencing analysis

Abstract Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma characterized by the COL1A1‐PDGFB fusion gene. This study utilized single‐cell RNA sequencing to dissect the cellular and molecular landscape of primary DFSP. Distinct DFSP cell clusters, exhibiting fibroblast‐like traits, revealed variations in pathways associated with proliferation, inflammation and metabolism. Differential gene expression analysis during the differentiation from tumour stem cells to DFSP cells unveiled SMOC2, DCN and TGFBR3 as potential regulators of tumour invasion and immune infiltration through VEGF/TGF‐β signalling modulation. Cellular communication analysis highlighted interactions within DFSP cell clusters and with endothelial cells, implicating molecules such as NAMPT, ANGPT2 and PTN in pathogenesis and treatment resistance. These findings offer insights into DFSP intratumour heterogeneity, elucidate molecular mechanisms underlying tumour behaviour, and suggest potential therapeutic targets.