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

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.

Figure 1

Workflow of this study.

Figure 2

Expression level and prognostic significance of HAUS1 in glioma. (a) Expression level of HAUS1 in glioma and normal tissues based on the GTEx and TCGA databases. Kaplan–Meier survival curves of (b) OS based on GTEx and TCGA databases and (c) OS based on the CGGA database. Kaplan–Meier survival curves of (d) DSS and (e) PFI based on the GTEx and TCGA databases. ROC curves demonstrate that the AUC values for predicting 1-, 3-, and 5-year (f) OS of patients are 0.751, 0.815, and 0.756, respectively, (g) disease-specific survival of patients are 0.750, 0.807, and 0.771, respectively, and (h) progression-free interval of patients are 0.741, 0.718, and 0.705, respectively, based on TCGA and GTEx databases. (i) ROC curves reveal that the AUC values for predicting 1-, 3-, and 5-year OS of patients are 0.641, 0.716, and 0.725, respectively, based on the CGGA database.

Figure 3

(a) Univariate Cox analysis of HAUS1 and different clinical variables. (b) Multivariate Cox analysis of HAUS1 and various clinical variables. (c) A nomogram integrating HAUS1 and other clinical variables based on TCGA database. (d) Calibration curve of the nomogram.

Figure 4

Relationship between HAUS1 expression and WHO grades (grade II, III, and IV) based on (a) mRNAseq_325 in CGGA, (b) mRNAseq_693 in CGGA, and (c) TCGA. Differences in HAUS1 expression levels among tumour samples from patients with glioma of different grades. (d) The different expression of HAUS1 in low MGMT methylation group (G1) and high MGMT methylation group (G2). (e) Representative western blot images of HAUS1 and GAPDH from three groups. GAPDH was used as a protein-loading control. Relative protein levels of HAUS1 in the three groups are expressed as mean ± S.E.M of three independent experiments (^∗P < 0.05, ^∗∗P < 0.01). (f) qRT-PCR results showing significant differences in mRNA expression of HAUS1; data are expressed as fold change compared to the NORM group and as mean ± SEM of three independent experiments (^∗∗P < 0.01, ^∗∗∗∗P < 0.0001).

Figure 5

Relationship between HAUS1 expression and IDH mutation status based on (a) mRNAseq_325 in CGGA, (b) mRNAseq_693 in CGGA, and (c) TCGA and 1p/19q codeletion status based on (d) mRNAseq_325 in CGGA, (e) mRNAseq_693 in CGGA, and (f) TCGA. Correlation between HAUS1 expression level and (g) proliferation marker (Ki-67 expression) and (h) invasion marker (vimentin expression).

Figure 6

Survival analysis of patients with glioma in the high and low HAUS1 expression groups based on (a) IDH mutation status, (b) chemotherapy, (c) radiotherapy, and (d) 1p/19q codeletion status in the CGGA dataset.

Figure 7

PPI networks and functional enrichment analyses. (a) A PPI network of HAUS1 and its co-expressed genes constructed using the STRING database. (b) Functional enrichment analyses of HAUS1 and its co-expressed genes. (c–l) Correlation between HAUS1 expression and its co-expressed genes.

Figure 8

(a) Volcano plot of differentially expressed genes (DEGs) in TCGA dataset. (b) Heat map of DEGs in TCGA dataset.

Figure 9

Functional enrichment analyses of HAUS1 using (a) KEGG and (b) GO analysis in TCGA dataset.

Figure 10

The proportion of 22 types of tumour-infiltrating lymphocytes in the high- and low-HAUS1-expression groups in (a) TCGA and (b) CGGA datasets. Red represents elevated expression, and blue represents reduced expression.

Figure 11

Heatmap of 22 types of tumour-infiltrating lymphocytes based on (a) TCGA and (b) CGGA. (c) The association between HAUS1 expression level and various monocytes markers.

Figure 12

Relationship between HAUS1 expression and immune checkpoints.