Abstract
Purpose: Tumor necrosis factor receptor-associated protein 1 (TRAP1) is essential for carcinogenesis and the advancement of cancer, making it a promising therapeutic target in oncology. Nevertheless, comprehensive bioinformatic analyses of TRAP1 across diverse cancer types are limited. Herein, we analyzed TRAP1 across all cancer types, focusing on its expression in relation to prognosis, immune infiltration, and the mammalian target of rapamycin and receptor tyrosine kinase signaling pathways. Methods: We evaluated TRAP1’s clinical relevance for prognostic predictions and its association with tumor immunity and metabolism. TRAP1’s function in hepatocellular carcinoma cell invasion, migration, and proliferation was examined in vitro using wound healing assays and the cell counting kit-8; apoptosis was examined through reactive oxygen species detection. Results: We found that TRAP1 significantly predicts cancer prognosis and is closely linked to immune and metabolic tumor characteristics. In liver cancer cells, TRAP1 knockdown prevented invasion, migration, and proliferation; increased reactive oxygen species; and promoted apoptosis. Conclusion: In summary, this study reveals the critical clinical significance of TRAP1 across multiple cancer types through a pan-cancer analysis. Further in vitro experiments demonstrate that knocking down TRAP1 significantly suppresses malignant phenotypes of tumor cells in hepatocellular carcinoma by inducing oxidative stress and apoptosis. Thus, TRAP1, particularly in liver cancer, represents a highly promising prognostic biomarker and a novel metabolic therapeutic target. These findings provide direction for subsequent research on TRAP1 and strongly support its potential for translational exploration in hepatocellular carcinoma treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s12672-025-04238-9.