背景:胶质瘤是一种发生在所有年龄段的脑肿瘤,但常见于成年人。尽管对肿瘤的理解有了进展,我们无法改善患者的生存率,也没有合适的预测进展和预后的生物标志物.碱基切除修复机制维持了基因组的完整性,防止肿瘤形成。然而,对细胞的持续化学损伤导致突变,这些突变逃避了修复机制并支持肿瘤生长。癌症中的肿瘤微环境对决定肿瘤生长至关重要。发展,以及对治疗的反应。本研究探讨了碱基切除修复基因(BER)在调节肿瘤微环境中的意义。
方法:我们使用来自癌症基因组图谱(TCGA)和基因表达综合(GEO)的公开数据集来探索碱基切除修复基因在调节肿瘤微环境中的作用。分析了碱基切除修复基因的表达数据,它们与免疫标记的相关性,他们的预后潜力,和富集分析,以了解它们在低度胶质瘤(LGG)进展中的调节途径。
结果:分析显示,BER基因在LGG的总体和无病生存中起着不可或缺的作用。像MUTYH这样的基因,PNKP,UNG和XRCC1与免疫浸润水平相关,与不同免疫细胞相关的各种免疫标志物显著相关。包括肿瘤相关的巨噬细胞。MUTYH,UNG和XRCC1与IDH1突变状态相关,和功能富集分析表明,这些基因富集在几个途径,如Wnt,PD-1和整合素信号传导。
结论:我们的发现表明BER基因MUTYH,PNKP,UNG和XRCC1可能是预后生物标志物,并与肿瘤微环境的免疫细胞高度相关。
BACKGROUND: 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.
CONCLUSIONS: 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.