High-expression of Galactosidase alpha is correlated with poor prognosis and immune infiltration in low-grade glioma

Abstract

Background: Galactosidase alpha (GLA), a member of galactosidase (GAL) family, contributes to cancer diagnosis and targeted therapy. Up to now, neither prognosis nor immune infiltration has been demonstrated in cases with low-grade glioma (LGG). In LGG, we investigated the association between GLA expression and immune infiltration levels. Methods: GLA expression levels in pan-cancer were evaluated utilizing the Oncomine database. In addition, GLA level was screened via analyzing the gene expression omnibus (GEO) data and the Cancer Genome Atlas (TCGA) data, and evaluated in LGG tissues and adjacent tissues by using qPCR. TIMER database was utilized for evaluating the correlation between GLA level and LGG immune infiltrates. A correlation was found between GLA levels and LGG immune infiltrates utilizing the TIMER database. Moreover, we then assessed the TIMER data to explore clinical outcome in multiple immune cells and the correction between GLA expression and immune markers. Results: The mRNA levels of GLA were upregulated in LGG tissues. GLA expression was associated with a poor outcome of patients with LGG. Additionally, the infiltration levels of several immune cells were obviously enriched in LGG with a higher GLA level. Moreover, LGG prognosis was worsened with high GLA levels in immune cells. Conclusions: These results suggested that GLA levels in LGG might be more predictive of immune infiltration, with potential value for assessment of tumor development.

Keywords: Galactosidase alpha; Immune infiltration; Low-grade glioma; Prognosis.

Figure 1

GLA expression analysis across pan-cancer and LGG. (A) Different expression levels of GLA between multiple tumor tissues and normal tissues by analyzing TCGA data. (B-C) Verification of GLA mRNA expression levels in LGG GSE4290 and GSE16011 dataset. (D) Scatter diagram of GLA mRNA levels in twenty-three pairs of LGG tissues and adjacent samples. **P<0.01, ***P<0.001.

Figure 2

Prognostic value of GLA level across pan-cancer and LGG. High expression level of GLA is related to worse overall survival in patients with ACC, LIHC, UVM, STAD, GBM or LGG. Samples with high GLA expression levels was labeled as red curve. Samples with low GLA expression levels was labeled as blue curve. HR, hazard ratio; TPM, Transaction per million.

Figure 3

GLA is associated with immune cell infiltration. (A-B) Correlation of GLA expression level with multiple immune cell infiltration levels in LGG. The immune cells we analyzed were B cells, myeloid dendritic cells, macrophages, monocyte, neutrophils, CD4⁺ T cells and CD8⁺ T cells. (C) Enrichment score of multiple immune cells in low GLA expression group and high GLA expression group. P<0.01, P<0.001.

Figure 4

Survival analysis of the association between clinical outcome and immune infiltrates. The results from TIMER database showing the correlation between GLA expression levels and infiltrating levels of B cells, CD8⁺ T cells, CD4⁺ T cells, macrophages, neutrophils, and dendritic cells in (A) LGG and (B) GBM samples.

Figure 5

Correlation analysis of GLA expression and immune infiltration markers in pan-cancer. Correlation between GLA level and multiple immune-related markers, including (A) CD86, (B) CSF1R, (C) CCL2, (D) CD68 and (E) IL10 in pan-cancer. Each blue circle represents a type of tumor. GBM sample was marked as green circle. LGG sample was marked as orange circle.

Figure 6

Correlation analysis of GLA expression and immune infiltration markers. Correlation between GLA level and multiple immune-related markers, including (A) NOS2, (B) IRF5, (C) PTGS2, (D) CD163, (E) VSIG4 and (F) MS4A4A in pan-cancer. Each blue circle represents a type of tumor. GBM sample was marked as green circle. LGG sample was marked as orange circle.