Prognostic value of m6A regulators and the nomogram construction in glioma patients

Abstract

Although N6-methyladenosine (m6A) has been implicated in various biological functions in human cancers, its role in predicting the prognosis of glioma remains unclear. In this study, the transcriptome expression profiles and the clinical data of 961 patients were derived from the Chinese Glioma Genome Atlas (CGGA). We comprehensively evaluated the association between the expression of m6A regulators and the prognosis of glioma and established a 3-gene (YTHDF2, FTO, and ALKBH5) risk signature using least absolute shrinkage and selection operator (LASSO) analysis. Patients with a high-risk signature had significantly adverse prognoses. Gene set enrichment analysis (GSEA) analysis revealed that the G2M checkpoint, MTORC1 signaling, epithelial mesenchymal transition, and PI3K-AKT-mTOR signaling were significantly enriched in the high-risk group. Univariate and multivariate Cox regression analyses confirmed the independent prognostic value of this risk signature. We then constructed a nomogram for individualized prediction of overall survival (OS) by integrating clinicopathological features (age, World Health Organization [WHO] grade), treatment information (radiotherapy, temozolomide therapy), and m6A risk signature. The calibration curves showed excellent agreement between the predicted and actual probabilities for the 1-, 3-, and 5-year OS, with a C-index of 0.780 in the training cohort and 0.717 in the validation cohort. Altogether, our study elucidated the important role of m6A regulators in glioma prognosis, which is valuable for the selection of therapeutic methods and clinical management of patients with glioma.

The PANoptosis-related signature indicates the prognosis and tumor immune infiltration features of gliomas

“…We compared our model with several other prognostic models to assess the importance of the PANoptotic score for predicting the prognosis of glioma. The results showed that the prediction accuracy of our model was better than other models that have been reported (Chen et al, 2021;Liu P. et al 2022;Zeng et al, 2022) (Figures 5D-F and Supplementary Figures S5A-F).…”

“…In previous studies, transcriptomics-based prognostic models for glioma have also been proposed. For example, Chen et al constructed a prognostic model of glioblastoma based on the function of STEAP (Six-transmembrane epithelial antigen of the prostate) family, STEAP2-and STEAP3-based prognostic risk score ( Chen et al, 2021 ); Zeng et al researched a prognostic model of glioma based on pyroptosis named pyroptosis-related risk signature (PRRS) ( Zeng et al, 2022 ); Liu P. et al (2022) proposed a prognostic model of glioma based on m6A regulators model called risk score, etc. The predictive performance of our constructed model was better than each of the above models by comparison of area under the ROC curve (AUC).…”

Exploration of biological significance of m6A-related genes in Wilms tumor

“…In other tumor studies, it was found that m6A in peripheral blood of patients with gastric cancer increased with the progression and metastasis of gastric cancer, but decreased signi cantly after surgery, suggesting that m6A level in peripheral blood is a promising noninvasive diagnostic biomarker for gastric cancer patients [22]. In the study of m6A RNA methylation in glioma, it was found that high expression of m6A was associated with poor prognosis and tumor grade [23]. In the study of urological malignancies, high levels of m6A RNA methylation in mRNA were found to promote prostate cancer progression by regulating subcellular protein localization, and patients with high m6A RNA methylation had poor survival bene ts [24].…”

Emerging Roles and Mechanisms of RNA Modifications in Neurodegenerative Diseases and Glioma

“…FTO’s influence extends to mitochondrial functions, affecting the expression of genes like SDHA and regulating the STAT3/FTO axis [ 138 ]. Prognostic studies suggest that FTO can predict poor outcomes in glioma patients, and inhibitors targeting FTO have shown promise in reducing tumorigenicity and aggressiveness in glioma models [ 139 , 140 , 141 , 142 ]. FTO expression is also linked to the decreased apoptosis and increased proliferation of glioma cells [ 143 ], and its inhibition suppresses GSC growth and self-renewal [ 112 ].…”