Evaluation of Significance of SERPINA3 and SPP1 in Driving Glioma Progression Through Dysregulation of Brain Inflammatory Pathway

Glioma is a highly aggressive malignancy with a poor prognosis, particularly in grade IV glioblastoma. The monitoring of disease progression remains challenging due to high heterogeneity in the tumour and a lack of progressive markers to keep track of the tumour progression. This scarcity of good progressive biomarkers has led us to search for better options. SERPINA3 and SPP1 were investigated as potential dual biomarkers reflecting tumour microenvironment and enabling assessment of progression. In silico analysis was conducted, where correlation analysis was performed to evaluate the cell-type specificity of SERPINA3 in astrocytes and SPP1 in microglial cells, with comparisons across other neural populations in both low-grade glioma and glioblastoma. Pan-cancer expression analysis was conducted to determine whether these biomarkers remain significantly elevated in glioma relative to other malignancies, including hepatocellular carcinoma, given their hepatic origin. Alzheimers disease datasets were analysed to verify the relevance in neurodegenerative diseases. The in-silico analysis revealed that SERPINA3 and SPP1 show astrocytic and microglial specificity, respectively, and exhibit their highest expression levels in glioma across cancers. Co-expression analysis further identified enrichment of immunoregulatory pathways alongside upregulated oxidative stress-associated markers, highlighting the functional relevance of these biomarkers within the glioma microenvironment.