Comprehensive exploration on the role of base excision repair genes in modulating immune infiltration in low-grade glioma

Abstract

Introduction

Glioma is a brain tumour occurring in all age groups but common in adults. Despite advances in the understanding of tumours, we cannot improve the survival of the patients and do not have an appropriate biomarker for progression and prognosis prediction. The base excision repair mechanism maintains the integrity of the genome, preventing tumour formation. However, continuous chemical damage to the cells results in mutations that escape the repair mechanism and support tumour growth. The tumour microenvironment in cancer is crucial in determining the tumour growth, development, and response to treatments. The present study explored the significance of Base Excision Repair genes (BER) in modulating the tumour microenvironment.

Methods

We used the publically available data sets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to explore the role of the base excision repair gene in the modulating tumour microenvironment. The data was analysed for the expression of base excision repair genes, their correlation with the immune markers, their prognostic potential, and enrichment analysis to understand the pathways they modulate in low-grade glioma (LGG) progression.

Results

The analysis showed BER genes contribute an integral role in the overall and disease-free survival of LGG. Genes like MUTYH, PNKP, UNG and XRCC1 showed a correlation with the immune infiltration levels and a significant correlation with various immune markers associated with different immune cells, including tumour-associated macrophages. MUTYH, UNG and XRCC1 correlated with IDH1 mutation status, and functional enrichment analysis showed that these genes are enriched in several pathways like Wnt, PD-1 and Integrin signalling.

Conclusion

Our findings suggest that the BER genes MUTYH, PNKP, UNG and XRCC1 can potentially be prognostic biomarkers and highly correlate with the immune cells of the tumour microenvironment.