Immune Characteristics and Prognosis Analysis of the Proteasome 20S Subunit Beta 9 in Lower-Grade Gliomas

Abstract

Glioma is a common intracranial malignancy in adults and has a high mortality due to its poor prognosis and high recurrence rate. Dysregulation of protein degradation is one of the main promoting factors in glioma development. As an indispensable unit of the proteasome, Proteasome 20S Subunit Beta 9 (PSMB9) is one of the major enzymes in ubiquitin-dependent protein degradation in cells. In addition, proteasomes also participate in a series of cellular processing, like immune regulation, nerve signal transduction, material transport through channels, cell adhesion, and various signaling pathways. However, the relationship between the PSMB9 expression and the occurrence of lower-grade glioma (LGG) is still unknown. First, we collected the RNA-seq and clinical information about LGG clinical samples from The Cancer Genome Atlas (TCGA) cohort, Chinese Glioma Genome Atlas (CGGA; including CGGAseq1 and CGGAseq2) cohort, and Gene Expression Omnibus (GEO; GSE16011, GSE61374, and Rembrandt) cohort. Then, these data were used for differential analysis, survival analysis, enrichment analysis, clinical model construction, etc. In addition, we combine immune-related data for immune-related analysis, including immune infiltration and immunotherapy. Through the above research, we have provided a new biomarker for LGG prognosis prediction and more comprehensively explained the role of PSMB9 in the development of LGG. This study determined that PSMB9 can be used as an immunotherapy target through the analysis of immune data, providing new ideas for the clinical treatment of LGG.

Multikinase inhibitors modulate non-constitutive proteasome expression in colorectal cancer cells

“…Thus, activation of PD-L1 gene expression coincided with the activation of immunoproteasome subunit expression following treatment with the inhibitor. Here it should be mentioned that upregulated PSMB8/9 expression correlated with increased efficacy of immune checkpoint inhibitors in melanoma ( Kalaora et al, 2020 ) and lower-grade glioma ( Liu et al, 2022 ). Interestingly, it has been shown that mutated forms of BRAF, NRAS, and KRAS can upregulate non-constitutive proteasome expression and reduce endoplasmic reticulum stress in multiple myeloma ( Shirazi et al, 2020 ).…”

PSMB2 plays an oncogenic role in glioma and correlates to the immune microenvironment

“…In glioma cells, tumor suppressor genes are ubiquitin-labeled and degraded by the 26S proteasome 29 . The 20S proteasome, as its catalytic core, plays an important role in the degradation process of glioma tumor suppressor genes 30 . The lack of the 20S proteasome subunit makes glioma cells easy for the immune system to clear.…”

Single-cell RNA sequencing combined with mendelian randomization analysis identifies putatively causal genes associated with Gastric cancer

“…For example, higher expression of PSMB9 tend to have better prognosis in breast invasive carcinoma (BRCA) 19 , ovarian serous cystadenocarcinoma (OV) 20 , and non-small cell lung cancer (NSCLC) 21 . However, higher expression of PSMB9 showed worse prognosis in lower-grade glioma (LGG) 22 . The study of PSMB9 in GC was still limited.…”