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

in Journal of biomolecular structure & dynamics by Jiajia Shi, Yanwei Fang, Zhuo Zuo, Yaxing Wang, Zhongqian Yin, Bin Jia, Zhouqi Yang, Zhe Wang, Zhenjun Guo, Yulong Sun

TLDR

  • The study identified CA9 as a biomarker for glioblastoma multiforme (GBM) sensitive to electric field (EF) therapy, and found that elevated EF intensity altered the conformation of the CA9 protein

Abstract

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.was identified as a differentially expressed gene (DEG) sensitive to EF stimulation in GBM using GEO and TCGA for integrated analysis. Elevatedexpression was associated with reduced overall survival in GBM patients, indicating that CA9 was an adverse prognostic factor. Single-cell data demonstrated thatexpression was significantly higher in GBM cells than in normal cells, suggesting that CA9 could be an EF-sensitive biomarker for GBM. GSVA analysis suggested thatwas related to hypoxia and glucose metabolism in glioblastoma. MD simulations were employed to examine the impact of EF (0 V/nm ≤≤ 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, thegene 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.

Overview

  • The study explored the underlying mechanism of electric field (EF) therapy in treating glioblastoma multiforme (GBM) using bioinformatics and molecular dynamics (MD) analysis
  • The study identified CA9 as a differentially expressed gene (DEG) sensitive to EF stimulation in GBM, and found that elevated expression was associated with reduced overall survival in GBM patients
  • The study used MD simulations to examine the impact of EF on the conformation of the CA9 protein, and found that elevated EF intensity altered the protein structure, affecting the motion of protein atoms

Comparative Analysis & Findings

  • The study identified CA9 as a biomarker for GBM sensitive to EF, with elevated expression associated with reduced overall survival in GBM patients
  • Single-cell data showed that CA9 expression was significantly higher in GBM cells than in normal cells, suggesting that CA9 could be an EF-sensitive biomarker for GBM
  • MD simulations showed that EF intensity affected the conformation of the CA9 protein, including reducing hydrogen bonds and altering the dipole moment

Implications and Future Directions

  • The study suggests that CA9 is a potential target for therapeutic interventions in EF-mediated GBM treatment
  • Future studies could investigate the clinical implications of using CA9 as a biomarker for GBM, and explore the potential therapeutic applications of EF therapy in combination with other treatments
  • The study highlights the need for further research into the molecular mechanisms underlying EF therapy in GBM, and the potential for combining EF therapy with other treatments to improve treatment outcomes
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