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

胶质瘤 癌症研究 流式细胞术 脑瘤 IDH1 生物标志物 生物 髓样 免疫学 医学 基因 病理 突变体 生物化学
作者
Luqing Tong,Jiabo Li,John Choi,Ayush Pant,Yuanxuan Xia,Christopher M. Jackson,Peidong Liu,Yi Li,Elias Boussouf,Michael Lim,Xuejun Yang
出处
期刊:Cancer Gene Therapy [Springer Nature]
卷期号:27 (9): 669-679 被引量:29
标识
DOI:10.1038/s41417-019-0140-8
摘要

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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