Abstract
DNA polymerase epsilon subunit 2 (POLE2) is a vital component of the DNA polymerase epsilon complex, essential for leading-strand DNA synthesis and maintaining genomic stability. Recent cancer studies have highlighted POLE2's oncogenic importance, as it is overexpressed in breast, lung, liver, and kidney cancers. Elevated POLE2 levels often correlate with poor overall and relapse-free survival, though some cancer types show contradictory associations, suggesting context-dependent roles. POLE2 is closely associated with the tumour microenvironment (TME), where higher levels link to lower immune and stromal scores, indicating an immunosuppressive TME. Additionally, POLE2 expression positively correlates with CD4+ memory and follicular helper T cells, while showing negative associations with regulatory T cells (Tregs), monocytes, mast cells, and M1 macrophages—highlighting its potential role in immune modulation. POLE2 also shows strong associations with immune checkpoint genes such as PD-L1 and CTLA-4, indicating a role in immune evasion mechanisms. Functional analyses further reveal its involvement in critical cellular pathways, including DNA replication, chromosomal segregation, cell cycle regulation, and DNA repair processes like mismatch repair and p53 signaling. Moreover, POLE2 is positively correlated with tumour mutational burden (TMB) and microsatellite instability (MSI), both of which are emerging biomarkers for immunotherapy responsiveness. Collectively, these insights position POLE2 as a promising prognostic and immunological biomarker with potential therapeutic relevance across multiple cancer types, warranting further in-depth investigation.
Keywords
Pan-cancer, Oncogenesis, POLE2, DNA polymerase, Tumour, Biomarker, Tumour microenvironment