Identifying α-KG-dependent prognostic signature for lower-grade glioma based on transcriptome profiles

• Published in: Frontiers in oncology 2022-07, Vol.12, p.840394-840394
• Main Authors: Zhang, Tan, Yuan, Liqun, Sheng, Minfeng, Chen, Yanming, Wang, Ji, Lan, Qing
• Format: Article
• Language: English
• Subjects: 2-HG; genome-wide analysis; IDH mutation; lower-grade glioma; Oncology; α-KG
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2022.840394

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.