Actin, connexin-43 and GAP-43 expression in gliomas: real-world associations with IDH status, tumor burden and survival.

BACKGROUND: Connexin-43 (Cx43), GAP-43 and actin are involved in cellular communication and cytoskeletal dynamics in gliomas, yet their clinical relevance remains largely unclear. We investigated their expression and association with survival and tumor characteristics in IDH-mutant and IDH-wildtype gliomas. METHODS: 134 adult patients operated for newly diagnosed gliomas WHO grades 2-4 in our center were included. Immunohistochemical expression of Cx43, GAP-43 and actin was assessed. Several clinical parameters, including progression-free (PFS) and overall survival (OS), were acquired from our institutional database. RESULTS: In IDH-wildtype tumors, higher Cx43 expression was associated with prolonged OS (p = 0.032). Whereas IDH-mutant gliomas showed significantly lower expression of Cx43 (p = 0.029) compared to IDH-wildtype tumors. Actin expression correlated with prognostically unfavorable higher WHO grade (p < 0.001), IDH-wildtype status (p < 0.001), preoperative contrast enhancement in MRI (p = 0.009) and decreased functional status (p < 0.001). Consequently, stronger actin expression was significantly associated with shorter PFS (7.2 vs. 17.4 months, p < 0.001) and OS (17.1 vs. 81.5 months, p < 0.001). Incidentally diagnosed tumors exhibited reduced GAP-43 expression (p = 0.012). None of the proteins was associated with perioperative complications. CONCLUSIONS: Upregulated actin expression is strongly linked to more aggressive glioma behavior and reduced survival. Higher Cx43 expression could sustain an onco-protective role in prognostically unfavorable IDH-wildtype tumors. These findings provide clinically relevant translational evidence for the role of cytoskeletal and connectivity-associated proteins in glioma biology.