Extracellular Matrix-Related Gene Signature Implied Immunosuppressive Status and Adverse Survival in Diffuse Glioma Patients

Background: Diffuse glioma is the most common and lethal primary malignant brain tumor, with a complicated tumor microenvironment reported. However, the role of the extracellular matrix (ECM) in diffuse gliomas remains unclear. Methods: To investigate the impact of ECM on glioma malignancy, we constructed an ECM-related signature with six selected prognosis-related genes (VTN, VCAN, TNC, LOXL1, EFEMP1, and AGRN) using the LASSO method. Results: This score was found to significantly differentiate between groups classified by clinical characteristics. Despite elevated immune infiltration and antigen release, the high-ECM-score group exhibited attenuated immune activation with profound exhaustion. Moreover, the ECM score demonstrated accurate prognostic predictive power across three independent validation datasets. Conclusions: Elevated ECM scores characterize an exhausted immune phenotype and are associated with a poorer prognosis in patients with diffuse glioma. This study enhances our understanding of the role of ECM in the malignant progression of gliomas.