Electric field-induced conformational dynamics of CA9: a potential biomarker for glioblastoma multiforme

GBM, a malignant brain tumor prevalent in adults, can be treated using Electric field (EF) therapy. However, the underlying mechanism of EF-based GBM therapy is not well understood. In this study, we used bioinformatics and MD analysis to explore CA9 in EF therapy for GBM. CA9 was identified as a differentially expressed gene (DEG) sensitive to EF stimulation in GBM using GEO and TCGA for integrated analysis. Elevated CA9 expression was associated with reduced overall survival in GBM patients, indicating that CA9 was an adverse prognostic factor. Single-cell data demonstrated that CA9 expression was significantly higher in GBM cells than in normal cells, suggesting that CA9 could be an EF-sensitive biomarker for GBM. GSVA analysis suggested that CA9 was related to hypoxia and glucose metabolism in glioblastoma. MD simulations were employed to examine the impact of EF (0 V/nm ≤ E ≤ 0.5 V/nm) on the conformation of the CA9 protein, including RMSF, RMSD, Rg, secondary structure, and dipole moment. The CA9 protein structure was altered with different EF intensities, affecting the motion of protein atoms in an EF intensity-dependent manner. The number of hydrogen bonds was significantly reduced as the EF intensity increased, indicating that EF disrupted the hydrogen bonds. Additionally, the EF intensity affected the dipole moment and characteristic time. Besides, the CA9 gene family analysis suggested that this gene family was highly conserved. Overall, CA9 showed potential as a GBM biomarker sensitive to EF, presenting a prospective target for therapeutic interventions in EF-mediated GBM treatment.