Abstract
Glioma is one of the most deadly types of brain cancer. As it is highly invasive, the prognosis for glioma patients remains dismal, with median survival rarely exceeding 16 months. Thus, developing a new prognostic biomarker for glioma and investigating its molecular mechanisms is necessary for the development of an efficient treatment strategy. In this study, we analyzed a cohort of 1,131 glioma patients using RNA-seq data from The Cancer Genome Atlas (TCGA project) and Gene Expression Omnibus (GSE4290 and GSE16011 datasets), and validated the results using the RNA-seq data of 1,018 gliomas from the Chinese Glioma Genome Atlas (CGGA project). We used the R language as the main tool for statistical analysis and data visualization. We found that NCAPG, a mitosis-associated chromosomal condensing protein, is highly expressed in glioma tissues. Furthermore, the expression of NCAPG increased significantly with the increase in tumor grade, and high NCAPG expression was found to be a predictor of poor overall survival in glioma patients (P < 0.001). This result shows that NCAPG expression could be an independent prognostic factor. Importantly, when the expression of NCAPG was knocked down, the CCK-8 assay revealed that the proliferation of glioma cells (LN-229 and T98G cell lines) decreased significantly compared with the control group. In addition, the healing rates of these cells were significantly lower in the si-NCAPG group than in the control group (P < 0.001). We then used the CIBERSORT algorithm to analyze the expression levels of 22 subpopulations of immune cells and found that NCAPG was significantly negatively correlated with natural killer cell activation. In addition, it was positively correlated with MHC-I molecules and ADAM17. Our study is first in comprehensively describing the high expression of NCAPG in glioma. It also shows that NCAPG can function as an independent prognostic predictor of glioma, and that targeting NCAPG can be a new strategy for the treatment of glioma patients.
Highlights
Glioma is the most common and aggressive primary malignant tumor of the central nervous system, accounting for 50–60% of intracranial tumors [1, 2]
The functional enrichment of differentially expressed genes and NCAPG in gliomas predicted that NCAPG may be closely related to the cell cycle [32], p53 signaling pathway [33], and PI3K/ARK signaling pathway [34] in glioma, which is consistent with previous studies on NCAPG
The results showed that high expression of NCAPG could decrease the survival rate of patients
Summary
Glioma is the most common and aggressive primary malignant tumor of the central nervous system, accounting for 50–60% of intracranial tumors [1, 2]. Glioma is usually associated with poor prognosis, with a 5-year survival rate of only 10–20% [6, 7]. With the development of molecular pathology, some molecular markers in glioma have played an important role in the diagnosis and prognosis of the disease, such as isocitrate dehydrogenase (IDH), epidermal growth factor receptor (EGFR), O-6-methylguanine-DNA methyltransferase (MGMT), and tumor protein p53 (TP53) [8]. In 2016, the WHO Classification of Tumors of the Central Nervous System (WHO CNS4) was first to use molecular markers in glioma classification, and in 2021 WHO CNS5 placed even more emphasis on their importance [9, 10]. The new molecular classification of glioma may play a key role in its prognosis
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