Department of Dermatology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.
Photomedicine Laboratory, Institute of Precision Medicine, Tsinghua University, Beijing, China.
Exp Dermatol. 2024 Aug;33(8):e15121. doi: 10.1111/exd.15121.
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.
隆突性皮肤纤维肉瘤（DFSP）是一种罕见的皮肤肉瘤，其特征是存在 COL1A1-PDGFB 融合基因。本研究利用单细胞 RNA 测序技术剖析了原发性 DFSP 的细胞和分子图谱。具有成纤维细胞样特征的不同 DFSP 细胞簇表现出与增殖、炎症和代谢相关的途径的变化。从肿瘤干细胞到 DFSP 细胞分化过程中的差异基因表达分析表明，SMOC2、DCN 和 TGFBR3 通过 VEGF/TGF-β 信号调节可能是肿瘤侵袭和免疫浸润的潜在调节剂。细胞通讯分析突出了 DFSP 细胞簇内以及与内皮细胞之间的相互作用，表明 NAMPT、ANGPT2 和 PTN 等分子在发病机制和治疗耐药性中起作用。这些发现深入了解了 DFSP 肿瘤内异质性，阐明了肿瘤行为的分子机制，并提出了潜在的治疗靶点。
