Cellular and molecular landscape of primary dermatofibrosarcoma protuberans: Insights from single-cell RNA sequencing analysis
Rui Peng
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
Search for more papers by this authorYingyi Li
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
Search for more papers by this authorYumei Gao
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
Search for more papers by this authorDian Chen
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
Search for more papers by this authorZhenghui Li
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
Search for more papers by this authorCorresponding Author
Yi Zhao
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
Correspondence
Yi Zhao, Department of Dermatology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Litang Road No 168, Changping District, Beijing 102218, China.
Email: [email protected]
Search for more papers by this authorRui Peng
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
Search for more papers by this authorYingyi Li
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
Search for more papers by this authorYumei Gao
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
Search for more papers by this authorDian Chen
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
Search for more papers by this authorZhenghui Li
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
Search for more papers by this authorCorresponding Author
Yi Zhao
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
Correspondence
Yi Zhao, Department of Dermatology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Litang Road No 168, Changping District, Beijing 102218, China.
Email: [email protected]
Search for more papers by this authorRui Peng and Yingyi Li should be considered joint first author.
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.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| exd15121-sup-0001-FileS1.docxWord 2007 document , 14.9 KB |
File S1. scRNA-seq protocol. |
| exd15121-sup-0002-FileS2.docxWord 2007 document , 2.6 MB |
File S2. Single-cell transcriptome processing data and cell cluster annotation. |
| exd15121-sup-0003-FileS3.docxWord 2007 document , 3 MB |
File S3. Cell markers identification, gene set enrichment analysis, and cell-cell communication analysis results. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Patel KU, Szabo SS, Hernandez VS, et al. Dermatofibrosarcoma protuberans COL1A1-PDGFB fusion is identified in virtually all dermatofibrosarcoma protuberans cases when investigated by newly developed multiplex reverse transcription polymerase chain reaction and fluorescence in situ hybridization assays. Hum Pathol. 2008; 39(2): 184-193. doi:10.1016/j.humpath.2007.06.009
- 2Trinidad CM, Wangsiricharoen S, Prieto VG, Aung PP. Rare variants of dermatofibrosarcoma protuberans: clinical, histologic, and molecular features and diagnostic pitfalls. Dermatopathology. 2023; 10(1): 54-62. doi:10.3390/dermatopathology10010008
- 3Llombart B, Monteagudo C, Sanmartín O, et al. Dermatofibrosarcoma protuberans: a clinicopathological, immunohistochemical, genetic (COL1A1-PDGFB), and therapeutic study of low-grade versus high-grade (fibrosarcomatous) tumors. J Am Acad Dermatol. 2011; 65(3): 564-575. doi:10.1016/j.jaad.2010.06.020
- 4Peng R, Zhang G, Li H. COL1A1-PDGFB fusion gene detection through bulk RNA-Seq and transcriptomic features of dermatofibrosarcoma protuberans. Dermatol Surg. 2023; 49(5S): S27-S33. doi:10.1097/DSS.0000000000003771
- 5Ge LL, Wang ZC, Wei CJ, et al. Unraveling intratumoral complexity in metastatic dermatofibrosarcoma protuberans through single-cell RNA sequencing analysis. Cancer Immunol Immunother. 2023; 72(12): 4415-4429. doi:10.1007/s00262-023-03577-2
- 6Haas BJ, Dobin A, Li B, Stransky N, Pochet N, Regev A. Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods. Genome Biol. 2019; 20: 213. doi:10.1186/s13059-019-1842-9
- 7Hao Y, Hao S, Andersen-Nissen E, et al. Integrated analysis of multimodal single-cell data. Cell. 2021; 184(13): 3573-3587.e29. doi:10.1016/j.cell.2021.04.048
- 8Aran D, Looney AP, Liu L, et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat Immunol. 2019; 20(2): 163-172. doi:10.1038/s41590-018-0276-y
- 9Hänzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-Seq data. BMC Bioinformatics. 2013; 14: 7. doi:10.1186/1471-2105-14-7
- 10Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov JP, Tamayo P. The molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst. 2015; 1(6): 417-425. doi:10.1016/j.cels.2015.12.004
- 11Ritchie ME, Phipson B, Wu D, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. doi:10.1093/nar/gkv007
- 12Cao J, Spielmann M, Qiu X, et al. The single cell transcriptional landscape of mammalian organogenesis. Nature. 2019; 566(7745): 496-502. doi:10.1038/s41586-019-0969-x
- 13Chen EY, Tan CM, Kou Y, et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013; 14: 128. doi:10.1186/1471-2105-14-128
- 14Jin S, Guerrero-Juarez CF, Zhang L, et al. Inference and analysis of cell-cell communication using CellChat. Nat Commun. 2021; 12: 1088. doi:10.1038/s41467-021-21246-9
- 15Muhl L, Genové G, Leptidis S, et al. Single-cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination. Nat Commun. 2020; 11(1): 3953. doi:10.1038/s41467-020-17740-1
- 16Mori T, Misago N, Yamamoto O, Toda S, Narisawa Y. Expression of nestin in dermatofibrosarcoma protuberans in comparison to dermatofibroma. J Dermatol. 2008; 35(7): 419-425. doi:10.1111/j.1346-8138.2008.00496.x
- 17West RB, Harvell J, Linn SC, et al. Apo D in soft tissue tumors: a novel marker for dermatofibrosarcoma protuberans. Am J Surg Pathol. 2004; 28(8): 1063-1069. doi:10.1097/01.pas.0000126857.86186.4c
- 18Gao Q, Mok HP, Zhuang J. Secreted modular calcium-binding proteins in pathophysiological processes and embryonic development. Chin Med J. 2019; 132(20): 2476-2484. doi:10.1097/CM9.0000000000000472
- 19Zhang W, Ge Y, Cheng Q, Zhang Q, Fang L, Zheng J. Decorin is a pivotal effector in the extracellular matrix and tumour microenvironment. Oncotarget. 2018; 9(4): 5480-5491. doi:10.18632/oncotarget.23869
- 20Pawlak JB, Blobe GC. TGF-β superfamily co-receptors in cancer. Dev Dyn. 2022; 251(1): 137-163. doi:10.1002/dvdy.338
- 21Wang YY, Hung AC, Lo S, Yuan SSF. Adipocytokines visfatin and resistin in breast cancer: clinical relevance, biological mechanisms, and therapeutic potential. Cancer Lett. 2021; 498: 229-239. doi:10.1016/j.canlet.2020.10.045
- 22Huang H, Bhat A, Woodnutt G, Lappe R. Targeting the ANGPT-TIE2 pathway in malignancy. Nat Rev Cancer. 2010; 10(8): 575-585. doi:10.1038/nrc2894
- 23Grzelinski M, Urban-Klein B, Martens T, et al. RNA interference-mediated gene silencing of pleiotrophin through polyethylenimine-complexed small interfering RNAs in vivo exerts antitumoral effects in glioblastoma xenografts. Hum Gene Ther. 2006; 17(7): 751-766. doi:10.1089/hum.2006.17.751
- 24Zhang L, Kundu S, Feenstra T, et al. Pleiotrophin promotes vascular abnormalization in gliomas and correlates with poor survival in patients with astrocytomas. Sci Signal. 2015; 8(406):ra125. doi:10.1126/scisignal.aaa1690
- 25Pleiotrophin WX. Activity and mechanism. Adv Clin Chem. 2020; 98: 51-89. doi:10.1016/bs.acc.2020.02.003
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