NCAPG Promotes Tumor Progression and Modulates Immune Cell Infiltration in Glioma

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.

Stemness-related gene signature for predicting therapeutic response in patients with esophageal cancer

“…NCAPG is one of the DESRGs selected to build the prediction model. Increased expression of NCAPG promotes oncogenesis in non-small cell lung cancer (51), glioma (52), lung adenocarcinoma (53), prostate cancer (54), and esophageal squamous cell carcinoma (55). NCAPG (log 2 FC =1.81; q value =2.68×10−11) was significantly upregulated in ESCA and positively correlated with resting NK cells, suggesting that human NK cells rest via the overexpression of NCAPG in ESCA.…”

NCAPG as a novel prognostic biomarker in numerous cancers: a meta-analysis and bioinformatics analysis

“…As eight studies did not record the hazard ratios (HRs) and/or Kaplan-Meier (K-M) curves for overall survival (OS), 11 articles were excluded from bioinformatics analysis. Finally, we included eight studies in the meta-analysis [5,6,8,9,12,[24][25][26], all of which were cohort studies, and all outcome measures were OS.…”

“…Due to the existence of heterogeneity, a subgroup analysis was performed to further explore the impact of high NCAPG expression on survival in different types of cancer (Figure 2). Four studies [5,9,25,26] investigated cancers of the respiratory system, two studies [8,24] investigated cancers of the digestive system, and the remaining two studies investigated other types of cancers, namely, glioma [12] and breast cancer [6]. According to the forest plot, upregulation of NCAPG expression in cancer tissues was related to worse OS regardless of the group (respiratory cancer, HR = 2.27, 95% CI = 1.73-2.98, P < 0.00001; digestive cancer, HR = 2.12, 95% CI = 1.39-3.22, P = 0.0005; breast cancer, HR = 7.57, 95% CI = 3.13-18.30, P < 0.00001; glioma, HR = 9.34, 95% CI = 3.75-23.26, P < 0.00001).…”

“…However, its role in various types of tumors remains controversial. For example, NCAPG is overexpressed in hepatocellular carcinoma [11] and glioma [12] but underexpressed in out-of-niche primary tumor cells of multiple myeloma and acute myeloid leukemia [13,14]. Therefore, we performed a meta-analysis to explore the relationship between NCAPG upregulation and the clinical characteristics of cancer, analyze the prognostic value of NCAPG for cancer patients, and validate its role by bioinformatics methods.…”

A mini-review of the role of condensin in human nervous system diseases

“…Wherein, NCAPG could be positively related to CDCA2 (cell division cycle-associated protein 2) in glioma, and the over-expression of NCAPG may regulate the cell cycle and promote the proliferation, migration, and invasion of glioma cells (Liang et al, 2016 ; Jiang et al, 2022 ; Jin et al, 2022 ). Meanwhile, NCAPG overexpression can also increase the expression of MHCI and AMAD17 molecules, both of which are located on the tumor surface, thus, assisting in camouflaging the tumor and preventing NK cells from being activated in the immune microenvironment (Zheng et al, 2022 ). In addition, the knocking down of NCAPG can make the tumor cells stay in the G1 phase of the cell cycle.…”