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POLD4 促进神经胶质瘤细胞增殖和抑制性免疫微环境:与实验验证相结合的泛癌症分析。

POLD4 Promotes Glioma Cell Proliferation and Suppressive Immune Microenvironment: A Pan-Cancer Analysis Integrated with Experimental Validation.

机构信息

Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.

出版信息

Int J Mol Sci. 2023 Sep 10;24(18):13919. doi: 10.3390/ijms241813919.

DOI:10.3390/ijms241813919
PMID:37762224
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10530695/
Abstract

POLD4 plays a crucial part in the complex machinery of DNA replication and repair as a vital component of the DNA polymerase delta complex. In this research, we obtained original information from various publicly available databases. Using a blend of R programming and internet resources, we initiated an extensive examination into the correlation between POLD4 expression and the various elements of cancers. In addition, we performed knockdown experiments in glioma cell lines to authenticate its significant impact. We discovered that POLD4 is upregulated in various malignant tumors, demonstrating a significant correlation with poor patient survival prognosis. Using function analysis, it was uncovered that POLD4 exhibited intricate associations with signaling pathways spanning multiple tumor types. Subsequent investigations unveiled the close association of POLD4 with the immune microenvironment and the effectiveness of immunotherapy. Drugs like trametinib, saracatinib, and dasatinib may be used in patients with high POLD4. Using experimental analysis, we further confirmed the overexpression of POLD4 in gliomas, as well as its correlation with glioma recurrence, proliferation, and the suppressive immune microenvironment. Our research findings indicate that the expression pattern of POLD4 not only serves as a robust indicator of prognosis in cancer patients but also holds promising potential as a new focus for treatment.

摘要

POLD4 作为 DNA 聚合酶 δ 复合物的重要组成部分,在 DNA 复制和修复的复杂机制中起着至关重要的作用。在这项研究中,我们从各种公开可用的数据库中获取原始信息。我们使用 R 编程和互联网资源的组合,对 POLD4 表达与癌症各要素之间的相关性进行了广泛的研究。此外,我们在神经胶质瘤细胞系中进行了敲低实验,以验证其显著影响。我们发现 POLD4 在各种恶性肿瘤中上调,与患者预后不良显著相关。通过功能分析,揭示了 POLD4 与跨越多种肿瘤类型的信号通路之间存在复杂的关联。随后的研究揭示了 POLD4 与免疫微环境的密切关联以及免疫治疗的有效性。像 trametinib、saracatinib 和 dasatinib 这样的药物可能对 POLD4 高表达的患者有用。通过实验分析,我们进一步证实了 POLD4 在神经胶质瘤中的过表达及其与神经胶质瘤复发、增殖和抑制性免疫微环境的相关性。我们的研究结果表明,POLD4 的表达模式不仅是癌症患者预后的有力指标,而且有可能成为治疗的新焦点。

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