Single-cell transcriptomic analysis identifies downregulated phosphodiesterase 8B as a novel oncogene in IDH-mutant glioma

单细胞转录组分析确定下调的磷酸二酯酶 8B 是 IDH 突变型胶质瘤中的一种新致癌基因

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作者:Zongze He #, Yu Peng #, Duo Wang #, Chen Yang, Chengzhi Zhou, Bo Gong, Siyuan Song, Yi Wang

Discussion

Crucially, the metabolic enzyme phosphodiesterase 8B (PDE8B) was found to be exclusively expressed and progressively downregulated in astrocytes and OPCs in higher-grade gliomas. This decreased expression identifies PDE8B as a metabolism-related oncogene in IDH-mutant glioma, marking its dual role as both a protective marker for glioma grading and prognosis and as a facilitator in glioma progression.

Methods

In this study, we undertook single-cell transcriptome sequencing of these glioma grades to elucidate their cellular and metabolic distinctions. Following the identification of cell types, we compared metabolic pathway activities and gene expressions between high-grade and low-grade gliomas.

Results

Notably, astrocytes and oligodendrocyte progenitor cells (OPCs) exhibited the most substantial differences in both metabolic pathways and gene expression, indicative of their distinct origins. The comprehensive analysis identified the most altered metabolic pathways (MCPs) and genes across all cell types, which were further validated against TCGA and CGGA datasets for clinical relevance.

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