Invasion/metastasis-related differentially methylated genes predict prognosis in diffuse gliomas

Area of Science:

• Neuro-oncology
• Epigenetics
• Cancer Genomics

Background:

• Diffuse gliomas are aggressive brain tumors with variable prognoses.
• Identifying reliable prognostic markers is crucial for patient stratification and treatment planning.
• DNA methylation plays a significant role in cancer development and progression, including invasion and metastasis.

Purpose of the Study:

• To identify differentially methylated genes (DMGs) related to invasion and metastasis in diffuse gliomas.
• To develop a DNA methylation-based risk model for prognostic stratification.
• To explore the biological insights and clinical relevance of these methylation markers.

Main Methods:

• Integrated gene expression and DNA methylation data from public glioma datasets.
• Screened for prognostic DMGs using Cox regression and log-rank tests.
• Constructed and validated a risk model using survival analysis and time-dependent ROC curves.
• Performed functional enrichment, immune infiltration, mutation, and clinical correlation analyses.
• Validated key genes (ERRFI1, MYO1G) in glioma cell lines.

Main Results:

• Identified 12 prognostic DMGs, with ERRFI1 and MYO1G forming a predictive risk model.
• The risk model demonstrated prognostic value in training and independent validation cohorts.
• The methylation signature correlated with adaptive immune and inflammatory responses.
• High-risk patients exhibited poorer overall survival, altered immune infiltration, and increased immune checkpoint expression.
• Knockdown of ERRFI1 or MYO1G suppressed glioma cell proliferation, invasion, and migration.

Conclusions:

• An invasion/metastasis-related DNA methylation signature based on ERRFI1 and MYO1G was identified.
• This signature offers complementary prognostic information for diffuse gliomas.
• The findings provide biological insights into glioma progression and potential therapeutic targets.