EYA3 is associated with an unfavorable outlook and is crucial for cellular growth in low-grade gliomas

Eyes absent (EYA) proteins, known for their critical role as regulators, are prominently expressed during embryogenesis but are typically downregulated following development. Notably, aberrant expression of Eya proteins has been observed in various tumor types. For example, studies on gastric cancer have shown that high EYA1 expression inhibits autophagy and activates the mTORC1 signaling pathway, thus promoting tumor cell growth; however, its impact on low-grade gliomas (LGGs) remains to be elucidated. This study investigated the involvement of EYA transcriptional coactivator and phosphatase 3 (EYA3) in LGG. Pan-cancer and survival analyses were performed to screen for EYA3 in LGGs. Subsequently, we systematically analyzed the association between EYA3 and multiple parameters, including prognosis, clinical characteristics, biological functions, genetic variations, and immunological characteristics of LGG. The tumor-promoting effects of EYA3 were evaluated using CCK8 and transwell assays. Western blotting and RT-qPCR were performed to assess the effects of EYA3 on the JAK2-STAT3-MYC axis. EYA3 is upregulated in various tumor types and is associated with poor prognosis. In LGG, patients with higher EYA3 levels had worse prognoses than those with lower EYA3 levels. EYA3 is associated with multiple adverse clinical traits and serves as an ‌independent prognostic factor for LGG. Furthermore, EYA3 expression in LGG was associated with immune checkpoint genes (ICPGs), tumor mutation burden (TMB), and immune cell infiltration. Laboratory studies have confirmed that abnormally elevated levels of EYA3 are necessary for the growth and cancerous characteristics of LGGs. EYA3 could be a novel therapeutic target and predictive biomarker for patients with LGGs, with abnormal expression linked to poor outcomes. Functionally, EYA3 enhances the malignant progression of LGGs, at least in part via engagement with the pharmacologically linked JAK2-STAT3-MYC signaling axis.