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CLEC5A expressed on myeloid cells as a M2 biomarker relates to immunosuppression and decreased survival in patients with glioma

Cancer Gene Therapy volume 27, pages 669–679 (2020)Cite this article

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Abstract

Glioma is the most common tumor in the central nervous system that portends a poor prognosis. Key genes negatively related to survival may provide targets for therapy to improve the outcome of glioma. Here, we report a protein-coding gene CLEC5A, which is the top 1 gene by univariate Cox regression analysis of 524 primary GBM samples. Expression of CLEC5A is significantly correlated with decreased overall survival in patients with glioma via large-scale analysis. An analysis of 2589 patient samples showed that CLEC5A expression is higher in (1) glioblastoma than in lower-grade glioma and nontumor tissue, (2) in the mesenchymal subtype than in other subtypes, and (3) in IDH1-wild type glioblastoma than in IDH1-mutated glioblastoma. Notably, this tumor-associated biomarker is expressed preferentially on myeloid cells over glioma cells. And it shows a strong co-expression with M2 macrophage biomarker. Furthermore, CLEC5A-associated genes are enriched in immunosuppressive biological processes. The silico flow cytometry also showed CLEC5A expression related to less tumor purity and more tumor-promoting leukocytes infiltration. In conclusion, we proposed a new M2 biomarker expressed on myeloid cells that may decrease survival in patients with glioma through immunosuppressive mechanisms.

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Acknowledgements

We thank the teams of the TCGA, CGGA, REMBRANDT and GSE16011. We also thank the online tool providers, including Betastasis, R2, GEPIA, CCLE, CIBERSORT, and Morpheus.

Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81872063) and the State Scholarship Fund from China Scholarship Council (No. 201806940031). ML is funded by Arbor, Aegenus, Altor, BMS, Accuray, and DNAtrix. This research received no external funding from these companies.

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Authors and Affiliations

  1. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China

    Luqing Tong, Jiabo Li, Peidong Liu, Li Yi & Xuejun Yang

  2. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Luqing Tong, John Choi, Ayush Pant, Yuanxuan Xia, Christopher Jackson, Elias Boussouf & Michael Lim

  3. Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China

    Luqing Tong, Jiabo Li, Peidong Liu, Li Yi & Xuejun Yang

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These authors contributed equally: Luqing Tong, Jiabo Li

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Tong, L., Li, J., Choi, J. et al. CLEC5A expressed on myeloid cells as a M2 biomarker relates to immunosuppression and decreased survival in patients with glioma. Cancer Gene Ther 27, 669–679 (2020). https://doi.org/10.1038/s41417-019-0140-8

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