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Proteomic analysis of pleomorphic dermal sarcoma reveals a fibroblastic cell of origin and distinct immune evasion mechanisms
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Proteomic analysis of pleomorphic dermal sarcoma reveals a fibroblastic cell of origin and distinct immune evasion mechanisms
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Journal Article
Proteomic analysis of pleomorphic dermal sarcoma reveals a fibroblastic cell of origin and distinct immune evasion mechanisms
2024
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
1-Phosphatidylinositol 3-kinase
/ Aged
/ Carcinoma, Squamous Cell - immunology
/ Carcinoma, Squamous Cell - metabolism
/ Carcinoma, Squamous Cell - pathology
/ Female
/ Fibroblastic differentiation
/ Humanities and Social Sciences
/ Humans
/ Male
/ Melanoma, Cutaneous Malignant
/ Microtubule-associated protein 1
/ PDS
/ Proteins
/ Sarcoma
/ Science
/ Skin
