The Inflammatory Characteristics of Symptomatic Glioma Associated With Poor Prognosis and Chemoresistance via Tumor Necrosis Factor Signaling Pathway

Background: Among gliomas, the most common primary malignant brain tumor, incidental gliomas account for 2.5%-5% of cases. The controversy over whether to pursue immediate treatment or adopt a wait-and-see approach remains, and more molecular and immunological evidence is needed for definitive treatment decisions.

Methods: Total RNA sequencing (RNA-seq) data and single cell RNA sequencing (scRNA-seq) data were retrospectively analyzed to compare the molecular and immunological tumor microenvironment differences between incidental glioma and symptomatic glioma samples. These were classified using symptom data from The Cancer Genome Atlas (TCGA) and public dataset.

Results: RNA-seq analysis of the GBMLGG dataset identified 343 genes upregulated in symptomatic glioma and 118 in incidental glioma, with 104 common genes upregulated in symptomatic glioma across both the TCGA and Chinese Glioma Genome Atlas (CGGA) datasets. Enrichment analysis revealed that these 104 genes in symptomatic glioma were significantly associated with immunological pathways. scRNA-seq analysis of glioma revealed 11 cell types, including T cells, myeloid cells, and oligodendrocytes, with the tumor necrosis factor (TNF) signaling pathway strongly influencing other cell types, particularly myeloid cells. Enrichment and survival analyses showed that TNF signaling is associated with temozolomide resistance and poorer prognosis in glioma patients.

Conclusion: The findings suggest that symptomatic glioma enhances inflammatory responses linked to poor prognosis and chemoresistance. This supports the hypothesis that immediate treatment of incidental glioma may improve patient outcomes over a wait-and-see approach.