Biological role and clinicopathological significance of leucine-rich α-2 glycoprotein 1 in the glioblastoma microenvironment

Pseudoprogression, often misinterpreted as glioblastoma progression on MRI, results from treatment-induced inflammation and can resolve without additional intervention. This study investigated the role of leucine-rich α-2 glycoprotein 1 (LRG1) in the glioblastoma microenvironment. Leucine-rich α-2 glycoprotein 1 is associated with inflammation and prognosis in various diseases and its blood concentrations reflect disease-related inflammation. We focused on LRG1 expression in reactive astrocytes and assessed its potential as a biomarker for glioblastoma pseudoprogression. Cases with high LRG1 expression exhibited a distinct molecular profile, with increased angiogenesis-related gene expression and reduced stem cell-related gene activity, underscoring its dual role in tumor biology and progression. In vitro experiments demonstrated that LRG1 suppressed tumor cell invasion, supporting its inverse correlation with tumor cell stemness. Immunohistochemical analysis revealed that astrocytic LRG1 was associated with heightened peritumoral inflammation, characterized by CD8+ T-cell infiltration at the tumor periphery; this correlated with higher pseudoprogression rates and poorer prognosis. By providing a histopathological marker for pseudoprogression, LRG1 complements current imaging modalities and offers a novel approach to addressing unresolved diagnostic challenges in glioblastoma. These findings establish LRG1 as a promising biomarker that could aid clinicians in distinguishing pseudoprogression from true progression, ultimately enhancing personalized treatment strategies for glioblastoma patients.