Pan-cancer multi-omics profiling reveals ubiquitin D as a novel biomarker for diagnosis, immune microenvironment remodeling and prognostic prediction.

Ubiquitin D (UBD), a key member of the ubiquitin-like modifier (UBL) family, plays a critical role in targeting proteins for proteasomal degradation. Current research indicates that UBD is frequently overexpressed in various malignancies, with its elevated expression closely correlated with disease progression in cancers such as gliomas, colorectal carcinoma, hepatocellular carcinoma, and breast cancer. In this study, we conducted a pan-cancer analysis of UBD to elucidate its prognostic significance, immunological roles, and potential clinical applications. Using data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and tools including Gene Expression Profiling Interactive Analysis (GEPIA2.0), CBio Cancer Genomics Portal (cBioPortal), University of Alabama at Birmingham CANcer data analysis Portal (UALCAN), Sangerbox and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), we analyzed UBD expression, prognosis, promoter methylation, genetic alterations, immune infiltration, and pathway enrichment. UBD was overexpressed in 29 cancer types, linking it to poor prognosis and higher histological grades. The most common type of genetic variation was gene amplification, and patients with these alterations exhibited significantly reduced overall survival rates. Epigenetically, 16 cancer types showed reduced UBD promoter methylation. UBD expression was significantly correlated with tumor microenvironment features, including immune infiltration, checkpoints, microsatellite instability (MSI), tumor mutational burden (TMB), and neoantigens (NEO). Pathway analysis implicated UBD in neurodegeneration, proteolysis, and apoptosis. Collectively, our study demonstrates that UBD is a promising prognostic biomarker and a potential predictor of immunotherapy sensitivity in multiple cancer types.