Molecular subtypes based on centrosome-related genes can predict prognosis and therapeutic responsiveness in patients with low-grade gliomas

Frontiers in Oncology

Oncology

Ke Cao¹  Xinyu Chen¹  Ganghua Zhang¹  Jianing Fang¹  Aiyan Chen¹  Panpan Tai¹ 

[1] Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, China;

关键词: centrosome;    LGG;    prognosis;    immunotherapy;    temozolomide;   

DOI  :  10.3389/fonc.2023.1157115

 received in 2023-02-02, accepted in 2023-03-07,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundAbnormalities in centrosome regulatory genes can induce chromosome instability, cell differentiation errors, and tumorigenesis. However, a limited number of comprehensive analyses of centrosome-related genes have been performed in low-grade gliomas (LGG).MethodsLGG data were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. The ConsensusClusterPlus” R package was used for unsupervised clustering. We constructed a centrosome-related genes (CRGs) signature using a random forest model, lasso Cox model, and multivariate Cox model, and quantified the centrosome-related risk score (centS). The prognostic prediction efficacy of centS was evaluated using a Receiver Operating Characteristic (ROC) curve. Immune cell infiltration and genomic mutational landscapes were evaluated using the ESTIMATE algorithm, single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm, and “maftools” R package, respectively. Differences in clinical features, isocitrate dehydrogenase (IDH) mutation, 1p19q codeletion, O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, and response to antitumor therapy between the high- and low-centS groups were explored. “pRRophetic” R packages were used for temozolomide (TMZ) sensitivity analysis. qRT-PCR verified the differential expression of the centrosomal gene team, the core of which is CEP135, between LGG cells and normal cells.ResultsTwo distinct CRG-based clusters were identified using consensus unsupervised clustering analysis. The prognosis, biological characteristics, and immune cell infiltration of the two clusters differed significantly. A well-performing centS signature was developed to predict the prognosis of patients with LGG based on 12 potential CRGs. We found that patients in the high-centS group showed poorer prognosis and lower proportion of IDH mutation and 1p19q codeletion compared to those in the low-centS group. Furthermore, patients in the high-centS group showed higher sensitivity to TMZ, higher tumor mutation burden, and immune cell infiltration. Finally, we identified a centrosomal gene team whose core was CEP135, and verified their differential expression between LGG cells and normal glial cells.ConclusionOur findings reveal a novel centrosome-related signature for predicting the prognosis and therapeutic responsiveness of patients with LGG. This may be helpful for the accurate clinical treatment of LGG.

【 授权许可】

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Copyright © 2023 Zhang, Tai, Fang, Chen, Chen and Cao