
Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)
Published: April 8, 2025
Glioma is the most common malignancy of central nervous system, characterised by its high invasiveness and recurrence, which significantly limit therapeutic outcomes. Energy metabolism reprogramming, especially mitochondrial dysfunction, plays a pivotal role in tumour growth, survival, progression. Mitochondria serve as hub for energy production biosynthesis, adapting through alterations oxidative phosphorylation, lipid metabolism, tricarboxylic acid cycle to meet metabolic demands gliomas. Gancao Nourishing-Yin (GCNY) decoction, traditional herbal compound, has demonstrated potential antitumour effects, particularly modulating pathways stress, are critical cell adaptation. Genomic data from glioma GWAS dataset Finnish R11 database eQTL 13 distinct brain regions were analysed using Summary-data-based Mendelian Randomization(SMR) identify glioma-associated genes. MitoCarta3.0, genes, was used pinpoint mitochondrial-related Differentially expressed genes (DEGs) human microglial cells treated with GCNY extracted GEO GSE210945 cross-referenced SMR results key Colocalisation analysis, validation TCGA database, survival functional annotations performed explore mechanisms action. Integration MitoCarta3.0 identified 19 linked gliomas, primarily involved amino fatty metabolism. Among these, CYB5R3 PICK1 emerged strong genetic links signals (PPH4 = 1). CYB5R3, upregulated associated enhanced elevated reactive oxygen species (ROS) production, poor outcomes (HR 2.23, P < 0.001). PICK1, despite being downregulated, showed context-dependent roles progression, expression worse prognosis 2.86, moderate predictive capacity one-year (AUC 0.695). This study highlights identifying regulators influenced GCNY. By pathways, including ROS phosphorylation activity, offers novel multitarget strategy therapy. These findings underscore importance target gliomas provide new insights into integrated management.
Language: Английский