In:
Frontiers in Surgery, Frontiers Media SA, Vol. 8 ( 2022-2-3)
Abstract:
Glioma is the most common primary brain tumor with a poor prognosis. Key genes that are negatively related to prognosis may provide the therapy targets to cure glioma. To clarify the role of CD44 in glioma, we explored its function at bulk-transcriptome, spatial and single-cell transcriptome levels. Methods In total, expression profiles with survival data of whole-grade glioma from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), RNA-seq data with anatomic information of glioblastoma (GBM) from the Ivy Glioblastoma Atlas Project, RNA-sequencing (RNA-seq) data from recurrent GBM receiving adjuvant anti -PD-1 immunotherapy accessed through GSE121810, and single-cell RNA-seq data of GBM under accession GSE103224 were enrolled in this study. CD44 -specific findings were further analyzed by R language. Results CD44 is positively correlated with WHO grade of malignancy and is negatively related to prognosis in glioma. Meanwhile, CD44 predominantly expresses in GBM mesenchymal subtype, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses reveal that CD44 positively coexpressed genes are closely related to glioma immunity. Moreover, CD44 + cells mainly distribute in perinecrotic region with high expression of immune factors. At single-cell resolution, only malignant tumor cells, tumor-associated macrophages (TAMs), and T cells express CD44 in GBM. CD44 + malignant tumor cells are in mesenchymal-1-like (MES1-like) cellular state, and CD44 + TAMs are in M2 phenotype. CD44 + T cells have high expression of both PD-1 and PD-L1 . CD44 and its directly interacted inhibitory immunomodulators are upregulated in patients with nonresponder recurrent GBM treated with PD-1 blockade therapy. Conclusion Our work demonstrates that CD44 , a new M2 TAM biomarker, is involved in immune suppressor and promote glioma progression in glioma microenvironment. These results expand our understanding of CD44 -specific clinical and immune features in glioma.
Type of Medium:
Online Resource
ISSN:
2296-875X
DOI:
10.3389/fsurg.2021.775194
DOI:
10.3389/fsurg.2021.775194.s001
DOI:
10.3389/fsurg.2021.775194.s002
DOI:
10.3389/fsurg.2021.775194.s003
DOI:
10.3389/fsurg.2021.775194.s004
DOI:
10.3389/fsurg.2021.775194.s005
DOI:
10.3389/fsurg.2021.775194.s006
DOI:
10.3389/fsurg.2021.775194.s007
DOI:
10.3389/fsurg.2021.775194.s008
DOI:
10.3389/fsurg.2021.775194.s009
DOI:
10.3389/fsurg.2021.775194.s010
DOI:
10.3389/fsurg.2021.775194.s011
DOI:
10.3389/fsurg.2021.775194.s012
DOI:
10.3389/fsurg.2021.775194.s013
DOI:
10.3389/fsurg.2021.775194.s014
DOI:
10.3389/fsurg.2021.775194.s015
DOI:
10.3389/fsurg.2021.775194.s016
DOI:
10.3389/fsurg.2021.775194.s017
DOI:
10.3389/fsurg.2021.775194.s018
DOI:
10.3389/fsurg.2021.775194.s019
DOI:
10.3389/fsurg.2021.775194.s020
DOI:
10.3389/fsurg.2021.775194.s021
DOI:
10.3389/fsurg.2021.775194.s022
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2773823-1
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