PDF(Pubmed)
Abstract：
Pleomorphic dermal sarcomas are infrequent neoplastic skin tumors, manifesting in regions of the skin exposed to ultraviolet radiation. Diagnosing the entity can be challenging and therapeutic options are limited. We analyzed 20 samples of normal healthy skin tissue (SNT), 27 malignant melanomas (MM), 20 cutaneous squamous cell carcinomas (cSCC), and 24 pleomorphic dermal sarcomas (PDS) using mass spectrometry. We explored a potential cell of origin in PDS and validated our findings using publicly available single-cell sequencing data. By correlating tumor purity (TP), inferred by both RNA- and DNA-sequencing, to protein abundance, we found that fibroblasts shared most of the proteins correlating to TP. This observation could also be made using publicly available SNT single cell sequencing data. Moreover, we studied relevant pathways of receptor/ligand (R/L) interactions. Analysis of R/L interactions revealed distinct pathways in cSCC, MM and PDS, with a prominent role of PDGFRB-PDGFD R/L interactions and upregulation of PI3K/AKT signaling pathway. By studying differentially expressed proteins between cSCC and PDS, markers such as MAP1B could differentiate between these two entities. To this end, we studied proteins associated with immunosuppression in PDS, uncovering that immunologically cold PDS cases shared a \"negative regulation of interferon-gamma signaling\" according to overrepresentation analysis.
摘要：
多形性真皮肉瘤是罕见的肿瘤性皮肤肿瘤，表现在暴露于紫外线辐射的皮肤区域。诊断实体可能是具有挑战性的,并且治疗选择是有限的。我们分析了20个正常健康皮肤组织（SNT）样本，27例恶性黑色素瘤（MM），20皮肤鳞状细胞癌（cSCC），和24多形性真皮肉瘤（PDS）使用质谱。我们探索了PDS中潜在的起源细胞，并使用公开可用的单细胞测序数据验证了我们的发现。通过关联肿瘤纯度(TP)，通过RNA和DNA测序推断，蛋白质丰度，我们发现成纤维细胞共享大多数与TP相关的蛋白质.也可以使用公开的SNT单细胞测序数据进行该观察。此外，我们研究了受体/配体（R/L）相互作用的相关途径。对R/L相互作用的分析揭示了cSCC中不同的途径，MM和PDS,PDGFRB-PDGFDR/L相互作用和PI3K/AKT信号通路的上调具有突出作用。通过研究cSCC和PDS之间的差异表达蛋白，MAP1B等标志物可以区分这两种实体。为此,我们研究了PDS中与免疫抑制相关的蛋白质，根据过度表达分析，发现免疫冷PDS病例具有“干扰素-γ信号传导的负调节”。
