Objective To explore the expression level and function of THBS1 in glioblastoma (GBM). Methods The data was extracted from the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA)_693、CGGA_325 and CGGA_301 datasets. Gene expression data were normalized to analyze the differential expression of THBS1 in low-grade gliomas and GBM, as well as its relationship with isocitrate dehydrogenase (IDH) mutations, 1p/19q codeletion, and survival prognosis. Based on single-cell sequencing data and spatial transcriptomic data, the distribution of THBS1 in glioma tissue was analyzed. The CellCall algorithm and MAGIC algorithm were used to explore the function of THBS1 in the cell-cell communication, THBS1 related genes and their functions. The CIBERSORTx algorithm was used to analyze the relationship between THBS1 and immune cell infiltration. Results The expression level of THBS1 in GBM tissue was higher than that in normal tissue, and the difference was statistically significant (P < 0.05). In the CGGA and TCGA datasets, the expression level of THBS1 in GBM patients was higher than that in low-grade gliomas, and the difference was statistically significant (both P < 0.01). The expression levels of THBS1 in IDH wild-type and 1p/19q non-codeletion patients were higher than those in IDH mutant and 1p/19q codeletion patients, respectively, and the differences were statistically significant (both P < 0.01). In the CGGA_693 and CGGA-325 datasets, the survival rate of patients with high expression of THBS1 gene was lower than that of patients with low expression, and the difference was statistically significant (P < 0.01). Single-cell sequencing data analysis showed that THBS1 was mainly expressed in monocyte/ macrophages of glioma tissue. Spatial transcriptome data analysis indicated that monocyte/ macrophages expressing THBS1 were spatially co-localized with astrocytes, tumor cells, neurons, oligodendrocytes, and oligodendrocyte precursor cells. The pathway activity and dependent ligand-receptor pathways of cell-cell communication between THBS1 negative and THBS1 positive monocytes/macrophages and tumor cells and neurons were different. Functional enrichment analysis showed that THBS1 related genes were involved in biological processes such as vesicle mediated transport, autophagy, and regulation of DNA-binding transcription factor activity. In the four datasets, the abundance of macrophage M0 in the high expression group of THBS1 was higher than that in the low expression group, and the difference was statistically significant (P< 0.05). Conclusions THBS1 is highly expressed in GBM and is associated with poor prognosis in patients. THBS1 regulates macrophage M0 infiltration, and monocytes/macrophages expressing THBS1 may regulate the microenvironment of GBM, thereby regulating oncogenesis.
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胡慧敏,李泽生,刘博涵,陈彦坤,彭大钊. THBS1 在胶质母细胞瘤中的表达及功能研究[J].神经疾病与精神卫生,2024,24(5): DOI :10.3969/j. issn.1009-6574.2024.05.003.