Comprehensive pan-cancer analysis of DIMT1 reveals its prognostic significance and immune-associated characteristics with experimental validation in gastric cancer

Abstract

Dimethyladenosine Transferase 1 (DIMT1) is an rRNA-modifying enzyme involved in ribosome biogenesis; however, its potential oncogenic relevance and immune-associated characteristics across human cancers remain incompletely understood. Here, we aimed to systematically characterize the biological and clinical significance of DIMT1 across malignancies. A comprehensive pan-cancer analysis was performed by integrating transcriptomic, genomic, and epigenetic data from TCGA and GTEx datasets. DIMT1 expression patterns, prognostic significance, genomic alterations, DNA methylation characteristics, and associations with the tumor immune microenvironment were systematically evaluated using multiple bioinformatics approaches. Functional enrichment and drug sensitivity analyses were further conducted in gastric cancer. In addition, in vitro and in vivo experiments were performed to investigate the biological effects of DIMT1 depletion in gastric cancer models. DIMT1 exhibited predominant nuclear localization and was aberrantly expressed across multiple cancer types. Elevated DIMT1 expression was associated with unfavorable survival outcomes in several malignancies. Pan-cancer analyses revealed distinct genomic and epigenetic alteration patterns and demonstrated significant associations between DIMT1 expression and immune infiltration profiles, immune regulatory genes, and cancer-type-specific TMB/MSI characteristics. In gastric cancer, DIMT1-associated genes were enriched in pathways related to RNA metabolism, cell-cycle regulation, and immune-related processes. Functional validation further demonstrated that DIMT1 silencing significantly inhibited gastric cancer cell proliferation, migration, and invasion in vitro and suppressed tumor growth in vivo. Our study provides a comprehensive characterization of DIMT1 across human cancers and identifies DIMT1 as a potential prognostic and immune-associated biomarker. Experimental validation further supports its tumor-promoting role in gastric cancer, highlighting DIMT1 as a candidate target for future therapeutic investigation.