Classification of Brainstem Gliomas Based on Tumor Microenvironment Status

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Brainstem gliomas (BSGs) present a challenge due to unknown tumor microenvironment (TME) heterogeneity.
• Understanding TME variations is crucial for developing effective BSG therapeutics.

Purpose of the Study:

• To investigate the inter-tumor heterogeneity of the TME in BSGs.
• To correlate TME characteristics with clinical profiles and biological features.
• To identify potential biomarkers for TME classification in BSGs.

Main Methods:

• Assessed TME status using pan-cancer gene expression signatures via single-sample gene set enrichment analysis (ssGSEA).
• Clustered TME subtypes using consensus clustering.
• Developed a four-gene panel and radiomics approach for TME classification.

Main Results:

• BSGs displayed significant TME heterogeneity, classified into four clusters: 'immune-enriched, fibrotic', 'immune-enriched, non-fibrotic', 'fibrotic', and 'depleted'.
• The 'fibrotic' cluster correlated with diffuse intrinsic pontine gliomas, and 'PA-like' tumors with 'immune-enriched, fibrotic' TME.
• The four TME clusters demonstrated distinct overall survival and independently influenced BSG outcomes.

Conclusions:

• BSGs exhibit substantial inter-tumor TME heterogeneity, leading to four distinct prognostic clusters.
• A four-gene panel and radiomics approach accurately identify these TME clusters, aiding clinical application and therapeutic development for brainstem gliomas.