Cancer Biology & Inflammatory Disorder Division, CSIR-IICB Translational Research Unit of Excellence, CN-6, Salt Lake, Sector - V, Kolkata, WB, 700091, India.
Laboratory Oncology, Dr. BRAIRCH, AIIMS, New Delhi, 110029, India.
Cell Mol Neurobiol. 2023 Oct;43(7):3753-3765. doi: 10.1007/s10571-023-01393-x. Epub 2023 Aug 6.
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.
POLD4 基因编码 DNA 聚合酶 delta 的一个亚基（δ4），该酶是参与 DNA 复制和修复的关键酶。最近的研究表明，POLD4 在某些癌症的发生中起着至关重要的作用。然而，关于 POLD4 在胶质母细胞瘤（GBM）中的作用知之甚少。因此，在这项研究中，我们使用了各种癌症生物信息学工具来探讨 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 基因表达并估计胶质母细胞瘤中的肿瘤浸润免疫细胞。使用 MEXPRESS 网络浏览器检索甲基化数据并进行分析。使用 UALCAN 网络服务器分析 POLD4 的蛋白质表达。使用 cBioPortal 和 GSEA 软件分别进行基因相关性和通路富集分析。然后进行生存分析。在 GBM 中，POLD4 在基因和蛋白质水平上均显著上调，ROC 曲线分析表明其是胶质母细胞瘤的潜在生物标志物。TCGA-GBM 泛癌症研究的 GSEA 分析表明，POLD4 表达与干扰素-γ反应、G2M 检查点、炎症反应、E2F 靶点、EMT 转换和 KRAS 信号通路等关键途径相关。此外，POLD4 表达与 3 个 CpG 位点的 DNA 甲基化呈正相关，包括 Cg16509978，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 OS、PFS 和 DFS 显著相关。我们还发现 POLD4 表达与改变的免疫细胞浸润有关。总之，POLD4 在胶质母细胞瘤中显著上调，可能作为 GBM 患者的潜在诊断或预后生物标志物。但是，需要进行大型队列研究来建立同样的结果。使用 TCGA 数据和上述各种癌症生物信息学工具，我们观察到胶质母细胞瘤患者的 POLD4 基因和蛋白质表达水平非常高。POLD4 的表达与炎症和致癌途径显著相关，并且与胶质母细胞瘤患者的不良预后也有显著相关性。
