Top-down stepwise refinement identifies coding and noncoding RNA-associated epigenetic regulatory maps in malignant...

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Malignant glioma diagnosis and prognosis increasingly rely on molecular biomarkers, moving beyond traditional histology.
• Existing research primarily focuses on coding genes, neglecting comprehensive analysis of both coding and noncoding RNA biomarkers and their regulatory networks.
• Detailed understanding of cross-talk signaling pathways among glioma biomarkers is limited.

Purpose of the Study:

• To identify novel diagnostic, prognostic, and therapeutic biomarkers for malignant glioma by analyzing coding and noncoding RNAs.
• To elucidate the complex regulatory mechanisms and cross-talk signaling pathways involving these biomarkers.
• To develop an accurate predictive model for malignant glioma.

Main Methods:

• Differential gene expression (DEG) and competing endogenous RNA (ceRNA) network analysis were performed.
• Cox and Lasso regression models were employed for biomarker identification and refinement.
• Integrated analysis included functional enrichment, single nucleotide variation (SNV), immune infiltration, transcription factor binding site analysis, and molecular docking.
• Cross-talk signaling pathways were investigated through logical reasoning and literature review.

Main Results:

• A novel predictive model comprising twelve noncoding RNAs (ncRNAs), one microRNA (miRNA), and six coding genes was developed with high accuracy (AUC 0.91, C-index 0.84 overall).
• The model demonstrated strong performance in specific glioma subtypes: Lower-grade glioma (LGG) (AUC 0.90, C-index 0.86) and Glioblastoma multiforme (GBM) (AUC 0.75, C-index 0.69).
• Identified cross-talk pathways are associated with circadian rhythm, tumor immune microenvironment, and cellular senescence.

Conclusions:

• The newly identified biomarkers offer potential for precise diagnosis, prognosis, and subclassification of malignant gliomas.
• The elucidated cross-talk signaling pathways provide insights into noncoding RNA-mediated epigenetic regulation in glioma tumorigenesis.
• These findings may facilitate the development of targeted therapeutic strategies for malignant glioma.