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HAUS奥格明样复合体亚基1影响胶质瘤的肿瘤微环境和预后结果。

HAUS Augmin-Like Complex Subunit 1 Influences Tumour Microenvironment and Prognostic Outcomes in Glioma.

作者信息

Yao Qi, Ge Xinqi, Lu Zhichao, Shi Jinlong, Shen Jianhong, Chen Jian

机构信息

Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China.

Department of Clinical Biobank, Affiliated Hospital of Nantong University, Nantong, China.

出版信息

J Oncol. 2022 Jul 12;2022:8027686. doi: 10.1155/2022/8027686. eCollection 2022.

Abstract

BACKGROUND

The expression of HAUS Augmin-like complex subunit 1 (HAUS1), a protein-coding gene, is low in normal samples among various cancers with pan-cancer analysis. The depletion of HAUS1 in cells decreases the G2/M cell compartment and induces apoptosis. However, the detailed expression pattern of HAUS1 and its correlation with immune infiltration in glioma (LGG and GBM) (LGG: low-grade glioma; GBM: glioblastoma) remain unknown. Therefore, in this study, we examined the role and prognostic value of HAUS1 in glioma.

METHODS

Transcriptional expression data of HAUS1 were collected from the CGGA and TCGA databases. The Kaplan-Meier analysis, univariate and multivariate Cox analyses, and receiver operating characteristic (ROC) curves were used to analyse the clinical significance of HAUS1 in glioma. The STRING database was used to analyse protein-protein interactions (PPI), and the "ClusterProfiler" package was used for functional enrichment analysis to examine the possible biological roles of HAUS1. In addition, the HAUS1 promoter methylation modification was analysed using MEXPRESS, and the association between HAUS1 expression and tumour-infiltrating immune cells was investigated using CIBERSORT.

RESULTS

Based on the data retrieved from TCGA (703 samples) and CGGA (1018 samples), an elevated expression of HAUS1 was observed in glioma samples, which was associated with poorer survival of patients, unfavourable clinical characteristics, 1p/19q codeletion status, WHO grade, and IDH mutation status. Furthermore, multivariate and univariate Cox analyses revealed that HAUS1 was an independent predictor of glioma. HAUS1 expression level was associated with several tumour-infiltrating immune cells, such as Th2 cells, macrophages, and activated dendritic cells. The outcomes of ROC curve analysis showed that HAUS1 was good to prognosticate immune infiltrating levels in glioma with a higher area under the curve (AUC) value (AUC = 0.974).

CONCLUSIONS

HAUS1 was upregulated and served as a biomarker for poor prognosis in patients with glioma. High HAUS1 expression was associated with several tumour-infiltrating immune cells such as Th2 cells, macrophages, and activated dendritic cells, which had high infiltration levels. Therefore, these findings suggest that HAUS1 is a potential biomarker for predicting the prognosis of patients with glioma and plays a pivotal role in immune infiltration in glioma.

摘要

背景

通过泛癌分析发现,蛋白质编码基因HAUS有丝分裂纺锤体组装因子样复合体亚基1(HAUS1)在各种癌症的正常样本中表达较低。细胞中HAUS1的缺失会减少G2/M期细胞区室并诱导细胞凋亡。然而,HAUS1在胶质瘤(低级别胶质瘤和胶质母细胞瘤)中的详细表达模式及其与免疫浸润的相关性仍然未知。因此,在本研究中,我们研究了HAUS1在胶质瘤中的作用和预后价值。

方法

从中国胶质瘤基因组图谱(CGGA)和癌症基因组图谱(TCGA)数据库收集HAUS1的转录表达数据。采用Kaplan-Meier分析、单因素和多因素Cox分析以及受试者工作特征(ROC)曲线分析HAUS1在胶质瘤中的临床意义。使用STRING数据库分析蛋白质-蛋白质相互作用(PPI),并使用“ClusterProfiler”软件包进行功能富集分析,以研究HAUS1可能的生物学作用。此外,使用MEXPRESS分析HAUS1启动子甲基化修饰,并使用CIBERSORT研究HAUS1表达与肿瘤浸润免疫细胞之间的关联。

结果

基于从TCGA(703个样本)和CGGA(1018个样本)检索到的数据发现,HAUS1在胶质瘤样本中表达升高,这与患者较差的生存率、不良的临床特征、1p/19q共缺失状态、世界卫生组织(WHO)分级和异柠檬酸脱氢酶(IDH)突变状态相关。此外,单因素和多因素Cox分析显示,HAUS1是胶质瘤的独立预测因子。HAUS1表达水平与多种肿瘤浸润免疫细胞相关,如辅助性T细胞2(Th2细胞)、巨噬细胞和活化的树突状细胞。ROC曲线分析结果显示,HAUS1对预测胶质瘤免疫浸润水平具有良好的效果,曲线下面积(AUC)值较高(AUC = 0.974)。

结论

HAUS1上调,是胶质瘤患者预后不良的生物标志物。HAUS1高表达与多种肿瘤浸润免疫细胞相关,如Th2细胞、巨噬细胞和活化的树突状细胞,这些细胞浸润水平较高。因此,这些发现表明,HAUS1是预测胶质瘤患者预后的潜在生物标志物,在胶质瘤免疫浸润中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6c4/9296284/d632c1723ee3/JO2022-8027686.001.jpg

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