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

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

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.

Keywords: DNA polymerase delta subunit 4 (POLD4); gliomas; immunomarker; immunosuppressive microenvironment; pan-cancer; proliferation.

MeSH terms

  • Cell Line
  • Cell Proliferation
  • DNA Polymerase III*
  • DNA Replication
  • Glioma* / genetics
  • Humans
  • Tumor Microenvironment / genetics

Substances

  • DNA Polymerase III
  • POLD4 protein, human