Abstract

Background: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is characterized by poor prognosis and marked molecular heterogeneity. Mitochondrial ribosomal proteins have emerged as regulators of cancer metabolism, yet the clinical significance of MRPL23 in GBM remains unclear. This study aimed to evaluate the prognostic relevance of MRPL23 expression in glioblastoma and its association with patient survival and mitochondrial functional profiles. Methods: MRPL23 protein expression was assessed by immunohistochemistry in tissue microarrays derived from 89 patients with primary glioblastoma and 36 samples of adjacent non-tumorous brain tissue. Survival analyses were performed using Kaplan–Meier estimates and Cox proportional hazards models. In silico validation was conducted using transcriptomic and proteomic data from 296 IDH-wildtype glioblastomas from The Cancer Genome Atlas. Correlation analyses were used to explore associations between MRPL23 expression and mitochondrial respiratory chain components. Results: MRPL23 protein expression was significantly upregulated in glioblastoma compared with non-tumorous brain tissue (p < 0.001). High MRPL23 expression was associated with significantly shorter overall survival in the institutional cohort (median 13.5 vs. 21 months, p = 0.013). Consistently, low MRPL23 expression in the TCGA cohort was associated with improved overall and progression-free survival. MRPL23 expression showed strong positive correlations with key mitochondrial respiratory chain proteins, including COX5B, UQCRC1, and COX4I1. Conclusions: MRPL23 is overexpressed in glioblastoma and is associated with unfavorable patient outcomes. These findings identify MRPL23 as a potential prognostic biomarker and highlight mitochondrial translation as a relevant biological process in aggressive glioblastoma.

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