UBE2A as a prognostic indicator across human cancers: Insights from multi-omics and immune landscape analyses

Abstract

Ubiquitin-conjugating enzyme E2A (UBE2A), a member of the ubiquitin-conjugating E2 enzyme family, has been implicated in tumor development; however, its role across human cancer types remains incompletely understood. The present study aimed to systematically characterize the expression pattern, prognostic importance and immune relevance of UBE2A in a pan-cancer context. Public datasets, including The Cancer Genome Atlas, Gene Expression Omnibus and Genotype-Tissue Expression, were integrated to evaluate UBE2A expression, clinical importance, molecular characteristics, immune associations and biological functions across cancer types. Single-cell RNA sequencing data were analyzed to investigate the cellular distribution of UBE2A. Functional validation was performed through UBE2A knockdown in breast cancer cell lines. Results indicated that UBE2A was significantly upregulated in a number of cancer types and was associated with unfavorable overall and progression-free survival. UBE2A expression exhibited significant correlations with immune cell infiltration and immune checkpoint-associated genes across cancer types. Functional enrichment analyses indicated that UBE2A was primarily involved in cell cycle regulation and proliferative processes. Single-cell analysis revealed preferential UBE2A expression in proliferative T-cell populations. Furthermore, in vitro experiments demonstrated that UBE2A knockdown significantly suppressed breast cancer cell proliferation, migration and invasion. Overall, UBE2A was shown to be a promising prognostic biomarker associated with tumor progression, cell cycle activity and immune-associated characteristics across cancer types. Its preferential expression in proliferative T-cell populations and oncogenic role in breast cancer suggest that UBE2A may serve as a potential therapeutic target and a candidate biomarker for evaluating tumor prognosis and the tumor immune microenvironment.