Comprehensive pan-cancer analysis of MEX3A in human tumors

Abstract

MEX3A is an evolutionarily conserved RNA-binding protein characterized by two KH RNA-binding domains and a C-terminal RING domain, suggesting potential roles in both post-transcriptional regulation and protein modification. Although MEX3A has been implicated in several individual cancer types, its shared and cancer-specific roles across human cancers remain incompletely understood. In this study, we performed a comprehensive pan-cancer analysis of MEX3A by integrating publicly available datasets, including TCGA, GTEx, CPTAC, and other external resources. We systematically evaluated MEX3A expression, genetic alterations, phosphorylation status, clinical relevance, RNA modification-related associations, immune-related features, and functional enrichment profiles across multiple tumor types. MEX3A was significantly upregulated in most cancers and showed associations with advanced pathological stage in several tumor types. Survival analyses indicated that elevated MEX3A expression was correlated with poor overall survival and disease-specific survival in cancers such as ACC, LIHC, MESO, and SARC, supporting its potential value as a prognostic biomarker. Genetic alteration analysis revealed frequent copy number amplification of MEX3A in several cancers, whereas these alterations were not consistently associated with survival outcomes. Proteomic analyses further identified altered phosphorylation levels at S338 and S462 in tumor tissues, suggesting that post-translational modification may contribute to the regulation of MEX3A activity in a cancer-type-specific manner. Correlation analyses showed that MEX3A expression was associated with RNA modification-related genes, immune modulators, immune checkpoint genes, tumor-infiltrating immune cells, tumor mutational burden, and microsatellite instability across different cancers. These findings suggest that MEX3A may participate in RNA regulatory networks and tumor-immune microenvironment interactions. Functional enrichment analysis revealed that MEX3A-associated proteins are involved in pathways related to transcriptional dysregulation, mRNA stability, and translational regulation. However, as these findings are primarily based on bioinformatic and correlation-based analyses, they should not be interpreted as evidence that MEX3A is a validated therapeutic or immunotherapy target. Overall, this study provides a systematic pan-cancer characterization of MEX3A and supports its potential role as a prognostic biomarker and a hypothesis-generating candidate for future mechanistic and clinical validation.