Background: The UBE2T gene encodes a ubiquitin-conjugating enzyme that plays a significant role in various cellular processes and malignancies. However, its specific function in stomach adenocarcinoma (STAD) remains poorly understood. This study aims to investigate the mechanisms of UBE2T on tumor cells and the tumor immune microenvironment (TME) in STAD via bioinformatics analysis and experimental validation.
Methods: RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA), and tumor microenvironment data were downloaded from the ESTIMATE database. Differential expression, correlation, and gene enrichment analyses were performed using R software. Immunohistochemistry (IHC) and Western Blotting were used to verify UBE2T expression in cancer versus normal tissues. Cell Proliferation, Colony Formation, and Transwell assays were conducted to evaluate cell proliferation, invasion, and migration capabilities.
Results: UBE2T was significantly upregulated in STAD tissues. In vitro studies confirmed that UBE2T promotes cell invasion, migration, and proliferation. UBE2T expression was correlated with the infiltration of diverse immune cells, showing positive associations with macrophages, T cells, and NK cells, while exhibiting negative correlations with B cells and monocytes. Furthermore, UBE2T exhibited significant negative correlations with most immune checkpoint genes, with the exception of TNFRSF25, TNFRSF18, and TNFSF9. High UBE2T expression was also associated with elevated Tumor Mutation Burden (TMB) and Microsatellite Instability (MSI).
Conclusions: UBE2T is closely linked to tumor progression, immune infiltration, checkpoint expression, and drug sensitivity in stomach adenocarcinoma. These findings suggest that UBE2T may influence tumor immunity and serve as a potential target for immunotherapeutic strategies.