Mannose Receptor C Type 2 Predicts Poor Outcome in Glioma and is Associated With Invasive Phenotypes and...

Glioma remains a lethal malignancy of the central nervous system, and additional biomarkers that improve prognostic stratification and inform therapeutic exploration are still needed. This study evaluated mannose receptor C-type 2 (MRC2/Endo180) by integrating public transcriptomic cohorts with in vitro validation. Expression profiles and matched clinical annotations were obtained from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project for tumor-normal comparisons and pan-cancer screening, and prognostic associations were further examined in the Chinese Glioma Genome Atlas (CGGA) cohort. MRC2 expression was assessed in glioma cell lines by reverse transcription quantitative PCR (RT-qPCR) and immunoblotting, and stable MRC2 knockdown was established in U87 and U251 cells using lentiviral short hairpin RNAs (shRNAs). Cell growth and clonogenicity were evaluated using CCK-8 and colony formation assays, whereas migration and invasion were assessed using porous-membrane insert assays. CDK4, CDK6, and β-catenin/epithelial-mesenchymal transition (EMT)-related markers were analyzed by immunoblotting. Across datasets, MRC2 was elevated in glioma, and higher expression was associated with worse overall survival, disease-specific survival, and progression-free interval. In vitro, MRC2 depletion reduced proliferation, clonogenicity, migration, and invasion, accompanied by decreased CDK4 and CDK6 protein levels and changes in β-catenin and EMT-related markers. Together, these findings support MRC2 as a candidate prognostic biomarker associated with aggressive glioma phenotypes and warrant further mechanistic and in vivo investigation.