Novel prognostic features and personalized treatment strategies for mitochondria-related genes in glioma patients

Abstract

BackgroundGliomas are the most common intracranial nervous system tumours that are highly malignant and aggressive, and mitochondria are an important marker of metabolic reprogramming of tumour cells, the prognosis of which cannot be accurately predicted by current histopathology. Therefore, Identify a mitochondrial gene with immune-related features that could be used to predict the prognosis of glioma patients.MethodsGliomas data were downloaded from the TCGA database and mitochondrial-associated genes were obtained from the MITOCARTA 3.0 dataset. The CGGA, kamoun and gravendeel databases were used as external datasets. LASSO(Least absolute shrinkage and selection operator) regression was applied to identify prognostic features, and area and nomograms under the ROC(Receiver Operating Characteristic) curve were used to assess the robustness of the model. Single sample genomic enrichment analysis (ssGSEA) was employed to explore the relationship between model genes and immune infiltration, and drug sensitivity was used to identify targeting drugs. Cellular studies were then performed to demonstrate drug killing against tumours.ResultsCOX assembly mitochondrial protein homolog (CMC1), Cytochrome c oxidase protein 20 homolog (COX20) and Cytochrome b-c1 complex subunit 7 (UQCRB) were identified as prognostic key genes in glioma, with UQCRB, CMC1 progressively increasing and COX20 progressively decreasing with decreasing risk scores. ROC curve analysis of the TCGA training set model yielded AUC (Area Under The Curve) values >0.8 for 1-, 2- and 3-year survival, and the model was associated with both CD8+ T cells and immune checkpoints. Finally, using cellMiner database and molecular docking, it was confirmed that UQCRB binds covalently to Amonafide via lysine at position 78 and threonine at position 82, while cellular assays showed that Amonafide inhibits glioma migration and invasion.ConclusionOur three mitochondrial genomic composition-related features accurately predict Survival in glioma patients, and we also provide glioma chemotherapeutic agents that may be mitochondria-related targets.

Prognostic relevance and validation of ARPC1A in the progression of low-grade glioma

“…Other mitochondrial oxidative-stress-related genes including CTSL, TXNRD2, NUDT1, STOX1, and CYP2E1 have been reported differentially expressed with potential prediction accuracy of glioma [57]. CMC1, COX20, and UQCRB are other mitochondrial genes specifically involved in the prognosis of glioma [37]. In addition to this, the cancer-promoting mechanisms of mitochondrial genes in other tumors are gradually being elucidated.…”

“…Hence, the metabolic reprogramming can be observed through the mitochondria in tumor cells depending on the microenvironment of the tumor. Mitochondrial-related genes have significant relation to the prognosis of glioma patients which requires substantial studies [37,38]. Unlike glioblastoma, LGG mainly develops in younger individuals [39].…”

Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their Secretome

“…Additionally, there is evidence that mitochondria are involved in cancer cell metastatic processes [98] and mitochondrial components, including proteins, are released within EVs, even though there are differences in the EV mitochondrial content [99]. Interestingly, radiation promotes the formation of EVs containing mitochondrial proteins from the PC3 (prostate cancer 3) cell line, which could likely enhance survival of these cells after their exposure to radiation [100].…”