Dual Roles of Signal Transducer and Activator of Transcription 1 (STAT1) in Cancer: Expression Patterns, Prognostic Significance, and Immune Associations Across Multiple Tumor Types.

BACKGROUND: Signal transducer and activator of transcription 1 (STAT1) is a pivotal transcription factor that plays a dual role in cancer biology. It behaves as a tumor suppressor and, under certain conditions, as a promoter. Few studies have analyzed STAT1 in pan-cancers and explored its role in cancer biology. This study aimed to investigate the expression of STAT1 across various cancers at different stages. Additionally, we examined the promoter methylation of STAT1 and its impact on STAT1 expression, evaluated the functional states of STAT1 in different cancer types, analyzed the correlation between STAT1 expression and survival prognosis, and studied the tumor immune infiltration. Furthermore, we analyzed STAT1 expression across diverse immune subsets in cancer. Subsequently, we conducted an analysis of STAT1-protein interactions and studied the cancer hallmarks of STAT1 and its related proteins. METHODS: Various bioinformatics tools (Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), Kaplan-Meier Plotter, StarBase, Enrichr, and Tumor and Immune System Interaction Database (TISIDB)) and databases (Cancer Single-cell State Atlas (CancerSEA) and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING)) were used in this study. We comprehensively investigated STAT1 protein expression across various types of cancer and the correlation between its expression and different tumor stages, DNA methylation, survival outcomes, and immune cell infiltration. Additionally, we examined the correlation between STAT1 expression and various immune subtypes of cancer, as well as the functional states of STAT1 in different cancer types. Moreover, we investigated the STAT1 protein interactions and cancer hallmarks of STAT1 and its related proteins. RESULTS: High STAT1 expression was found in 21 cancers and was differentially expressed across different clinical tumor stages and promoter methylation levels. In addition, we found that high expression correlated with better overall survival in some tumors, whereas it correlated with worse overall survival in other tumor types. Furthermore, the expression of STAT1 was associated with the level of immune infiltration in multiple tumors and different immune subtypes. We found that STAT1 expression had dual correlations (positive and negative) with different functional states in tumors, including angiogenesis and apoptosis. STAT1 protein interaction and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that 10 STAT1-interacting proteins were significantly enriched in cancer-related pathways. CONCLUSION: Our findings suggest that STAT1 may serve as a potential diagnostic and prognostic marker for several cancer types.