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Identifying α-KG-dependent prognostic signature for lower-grade glioma based on transcriptome profiles
The inhibition of alpha-ketoglutarate (α-KG)-dependent dioxygenases is thought to contribute to isocitrate dehydrogenase (IDH) mutation-derived malignancy. Herein, we aim to thoroughly investigate the expression pattern and prognostic significance of genes encoding α-KG-dependent enzymes for lower-g...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363673/ https://www.ncbi.nlm.nih.gov/pubmed/35965532 http://dx.doi.org/10.3389/fonc.2022.840394 |
Sumario: | The inhibition of alpha-ketoglutarate (α-KG)-dependent dioxygenases is thought to contribute to isocitrate dehydrogenase (IDH) mutation-derived malignancy. Herein, we aim to thoroughly investigate the expression pattern and prognostic significance of genes encoding α-KG-dependent enzymes for lower-grade glioma (LGG) patients. In this retrospective study, a total of 775 LGG patients were enrolled. The generalized linear model, least absolute shrinkage and selection operator Cox regression, and nomogram were applied to identify the enzyme-based signature. With the use of gene set enrichment analysis and Gene Ontology, the probable molecular abnormalities underlying high-risk patients were investigated. By comprehensively analyzing mRNA data, we observed that 41 genes were differentially expressed between IDH(MUT) and IDH(WT) LGG patients. A risk signature comprising 10 genes, which could divide samples into high- and low-risk groups of distinct prognoses, was developed and independently validated. This enzyme-based signature was indicative of a more malignant phenotype. The nomogram model incorporating the risk signature, molecular biomarkers, and clinicopathological parameters proved the incremental utility of the α-KG-dependent signature by achieving a more accurate prediction impact. Our study demonstrates that the α-KG-dependent enzyme-encoding genes were differentially expressed in relation to the IDH phenotype and may serve as a promising indicator for clinical outcomes of LGG patients. |
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