Comprehensive pan-cancer analysis unveils the significant prognostic value and potential role in immune microenvironment modulation of TRIB3.

TRIB3, a pseudokinase, was previously studied within only some specific cancer types, leaving its comprehensive functions in pan-cancer contexts largely unexplored. Here, we performed an integrated analysis of expression, prognosis, genetic alterations, functional enrichment and tumor immune-related characteristics in 33 cancer types. Our results showed that exhibits high expression levels across 24 different cancer types and correlates closely with unfavorable prognoses. Meanwhile, shows mutations in a wide spectrum of 22 distinct cancer types, with the predominant mutation types being missense mutations and gene amplifications, and significant changes in DNA methylation levels in 14 types of cancer. We further discovered that expression is significantly associated with cancer immune-related genome mutations, such as tumor mutational burden (TMB), microsatellite instability (MSI) and DNA mismatch repair (MMR), and infiltration of immunosuppressive cells, such as CD4 Th2 cells and myeloid-derived suppressor cells (MDSCs), into the tumor microenvironment. These results indicated that the expression of might reshape the tumor immune microenvironment (TIME) and lead to immunosuppressive "cold" tumors. In addition, our results confirmed that the loss of function of inhibits cell proliferation, promotes apoptosis, and leads to significant enrichment of "hot" tumor-related immune pathways, at least in breast cancer cells, which further supports the important role of in cancer prognosis and TIME regulation. Together, this pan-cancer investigation provided a comprehensive understanding of the critical role of in human cancers, and suggested that might be a promising prognostic biomarker and a potential target for cancer immunotherapy.