Retrospective analysis of real-world prognostic relevance of expression of actin, connexin-43, and GAP-43 in gliomas

Connexin-43 (Cx43), GAP-43, and actin are proteins involved in cellular communication and cytoskeletal dynamics in gliomas. A retrospective study at the Medical University of Innsbruck (Austria) investigated the association of expression of these proteins with survival and tumor characteristics in IDH-mutant and IDH-wildtype gliomas. The study included 134 adult patients operated for newly diagnosed gliomas WHO grades 2-4. Immunohistochemical expression of Cx43, GAP-43, and actin was assessed. In IDH-wildtype tumors, higher Cx43 expression was associated with prolonged overall survival (p=0.032), whereas IDH-mutant gliomas showed significantly lower expression of Cx43 compared to IDH-wildtype tumors (p=0.029). Actin expression correlated with prognostically unfavorable higher WHO grade (p<0.001), IDH-wildtype status (p<0.001), preoperative contrast enhancement on MRI (p=0.009), and decreased functional status (p<0.001). Stronger actin expression was significantly associated with shorter progression-free survival (median 7.2 versus 17.4 months; p<0.001) and shorter overall survival (median 17.1 versus 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. The authors conclude that upregulated actin expression is linked to more aggressive glioma behavior and reduced survival. Higher Cx43 expression could sustain an onco-protective role in prognostically unfavorable IDH-wildtype tumors.