POLD4基因编码DNA聚合酶δ4亚基，它是参与DNA复制和修复的关键酶。最近的研究表明，POLD4在某些癌症发展中起着至关重要的作用。然而，关于POLD4在胶质母细胞瘤（GBM）中的作用的知识缺乏。因此，在本研究中，我们使用了各种癌症生物信息学工具来探索POLD4在胶质母细胞瘤中的作用。从各种来源获取数据，以分析POLD4基因的表达并估计GBM中的肿瘤浸润免疫细胞。使用MEXPRESS网页浏览器检索和分析甲基化数据。使用UALCAN服务器分析POLD4的蛋白表达。使用cBioPortal和GSEA软件进行基因相关性和通路富集分析。随后进行生存分析。POLD4在GBM中基因和蛋白水平均显著上调，ROC曲线分析显示其作为胶质母细胞瘤潜在生物标志物。TCGA-GBM全癌症研究的GSEA分析显示，POLD4表达与干扰素γ响应、G2M检查点、炎症反应、E2F靶点、上皮-间质转化和KRAS信号通路等关键通路相关。此外，POLD4表达与3个CpG位点的DNA甲基化呈正相关，其中Cg16509978的Pearson相关系数值为0.398（p值≤0.01），而启动子区域呈正相关但不显著。此外，POLD4与不良生存、无进展生存和无病生存显著相关。我们还发现POLD4表达与免疫细胞浸润改变相关。总之，POLD4在胶质母细胞瘤中显著上调，并可能作为GBM患者的潜在诊断或预后生物标志物。然而，为了确立相同的结论，需要进行大样本队列研究。使用上述所述的TCGA数据和各种癌症生物信息学工具，我们观察到胶质母细胞瘤患者中POLD4基因和蛋白表达水平非常高。POLD4的表达与炎症和致癌通路显著相关，并且与胶质母细胞瘤患者不良预后也有显著相关性。© 2023. 作者（专利权人），独家授权给Springer Science+Business Media，LLC属于Springer Nature的一部分。

The POLD4 gene encodes a subunit (δ4) of DNA polymerase delta, which is a key enzyme involved in DNA replication and repair. Recent studies have suggested that POLD4 plays a crucial role in developing certain cancers. However, there is a lack of knowledge regarding the role of POLD4 in the context of glioblastoma (GBM). Therefore, in this study we have used various cancer bioinformatics tools to explore the role of POLD4 in glioblastoma. Data from various sources were accessed to analyze POLD4 gene expression and estimate tumor-infiltrating immune cells in glioblastoma. Methylation data were retrieved using the MEXPRESS web browser and analyzed. UALCAN webserver was used to analyze the protein expression of POLD4. Gene correlation and pathway enrichment analysis were performed using cBioPortal and GSEA software, respectively. Afterward, survival analysis was performed. POLD4 was significantly upregulated in glioblastoma at both gene and protein levels in GBM, and ROC curve analysis revealed it as a potential biomarker in glioblastoma. GSEA analysis of TCGA-GBM pan-cancer study exhibited that POLD4 expression was associated with critical pathways, such as interferon-gamma response, G2M checkpoint, inflammatory response, E2F targets, EMT transition, and KRAS signaling pathways. Furthermore, POLD4 expression was positively correlated with DNA methylation at 3 CpG sites, including Cg16509978, with a Pearson correlation coefficient value of 0.398 (p-value ≤ 0.01), while the promoter region had a positive correlation but was not significant. In addition, POLD4 is significantly linked with poor OS, PFS, and DFS. We also found association of POLD4 expression with altered immune cell infiltration. In conclusion, POLD4 is significantly upregulated in glioblastoma and may be used as a potential diagnostic or prognostic biomarker for GBM patients. However, to establish the same a large cohort study is needed. Using TCGA data and various cancer bioinformatics tools mentioned above we observed very high level of gene and protein expression of POLD4 in glioblastoma patients. The expression of POLD4 was significantly correlated with inflammatory and oncogenic pathways and it also has a significant correlation with adverse outcome in patients with glioblastoma.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.