TRIM33 is an antibody included in the myositis antibody spectrum, and its positivity is closely associated with dermatomyositis (DM), a type of idiopathic inflammatory myopathy characterized by skin and skeletal muscle involvement. Importantly, positive TRIM33 antibody signals a heightened risk of tumor occurrence, especially in adult dermatomyositis patients who have an increased tendency to be complicated with malignant tumors. In addition, TRIM33 is a key regulator of the homeostasis and function of multiple immune cell types, and numerous studies have found abnormal TRIM33 expression in various cancers. However, TRIM33 functions both as an oncogene and a tumor suppressor in these cancers, so this study aims to comprehensively investigate the potential molecular mechanisms and possible drug targets of TRIM33 in the pathogenesis and clinical prognosis of various human cancers, with a focus on its correlation with dermatomyositis and tumorigenesis.

We compared the TRIM33 expression profiles across various tumor types, incorporating survival and clinical feature analysis, genetic variation analysis, epigenetic analysis, immune and immunosuppressive cell infiltration analysis, gene co-expression, and gene alteration co-occurrence analysis. Additionally, protein-protein interaction (PPI) network and enrichment analysis, drug sensitivity analysis, and molecular docking studies were performed. Finally, in vivo and in vitro validations were conducted using mice and cell models to further explore the molecular mechanisms and potential drug targets of TRIM33.

The findings indicate that TRIM33 exhibits varying expression levels across different tumors, which impacts patient survival rates and correlates with specific clinical characteristics. Additionally, TRIM33 is characterized by genetic variations, including gene mutations, phosphorylation, and methylation. Furthermore, TRIM33 is associated with immune infiltration and immune cells, presenting distinct immune and molecular subtypes in certain tumors. Lastly, small molecule drugs that may influence TRIM33 activity have been identified.

TRIM33 shows abnormal expression in various tumors and plays a dual role (oncogene and tumor suppressor) in tumor development. Its expression level is closely related to patient survival and clinical characteristics, and it is involved in genetic variation, epigenetic regulation, and immune infiltration processes in tumors. The identified small molecule drugs targeting TRIM33, along with the clarified molecular mechanisms, provide a theoretical basis for TRIM33 to be used as a potential predictive and therapeutic target in various human cancers.