The pan-cancer landscape of RNA-binding protein MEX3A: A prognostic and immunological biomarker validated in gastric cancer

Background: The RNA-binding protein Muscle Excess 3A ( MEX3A ) is integral to post-transcriptional regulatory processes and has been implicated in carcinogenesis. However, a systematic pan-cancer analysis exploring its oncogenic potential, prognostic relevance, and involvement in the tumor immune microenvironment has to be elucidated. Methodoiogy: An integrated multi-omics approach was employed to investigate MEX3A across 33 cancer types using date from The Cancer Genome Atlas (TCGA). The analysis encompassed evaluation of expression profiles, prognostic significance, correlations with immune cell infiltration, immune checkpoint genes, mismatch repair (MMR) genes, and drug sensitivity. Key findings were subsequently validated in gastric cancer (STAD) using the GEO dataset (GSE19826), immunohistochemistry (IHC) on clinical samples, and in vitro functional assays including siRNA knockdown, CCK-8, wound healing, and Transwell experiments. Results: MEX3A was found to be significantly overexpressed in a range of malignancies and, was positively associated with advanced pathological stages. Elevated MEX3A levels were correlated with unfavorable clinical outcomes, including poorer overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in several cancer types, notably adrenocortical carcinoma (ACC), kidne renal clear cell carcinoma (KIRC), and LIHC. It demonstrated significant associations with immune cell infiltration, immune checkpoint expression, MMR gene expression, and sensitivity to specific anticancer agents. In gastric cancer, MEX3A was found to be markedly upregulated and associated with aggressive clinicopathological characteristics. Functional experiments demonstrated that MEX3A knockdown suppressed the proliferation, migration, and invasion of gastric cancer cells. Furthermore enrichment analysis revealed its potential involvement in key pathways such as the B-cell receptor signaling pathway and MHC class II-mediated immune responses. Conclusion: This study identifies MEX3A as a potent prognostic biomarker and a critical modulator of tumor immunity across various cancers. Its oncogenic role is further validated in gastric cancer, suggesting MEX3A as a promising therapeutic target for future investigation and the development of precision oncology interventions.