Abstract
The prognostic value of N6-methylandenosine-related long non-coding RNAs (m6A-related lncRNAs) was investigated in 646 lower-grade glioma (LGG) samples from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) datasets. We implemented Pearson correlation analysis to explore the m6A-related lncRNAs, and then univariate Cox regression analysis was performed to screen their prognostic roles in LGG patients. Twenty-four prognostic m6A-related lncRNAs were identified as prognostic lncRNAs and they were inputted in a least absolute shrinkage and selection operator (LASSO) Cox regression to establish a m6A-related lncRNA prognostic signature (m6A-LPS, including 9 m6A-related prognostic lncRNAs) in the TCGA dataset. Corresponding risk scores of patients were calculated and divided LGG patients into low- and high-risk subgroups by the median value of risk scores in each dataset. The m6A-LPS was validated in the CGGA dataset and it showed a robust prognostic ability in the stratification analysis. Principal component analysis showed that the low- and high-risk subgroups had distinct m6A status. Enrichment analysis indicated that malignancy-associated biological processes, pathways and hallmarks were more common in the high-risk subgroup. Moreover, we constructed a nomogram (based on m6A-LPS, age and World Health Organization grade) that had a strong ability to forecast the overall survival (OS) of the LGG patients in both datasets. We also establish a competing endogenous RNA (ceRNA) network based on seven of the twenty-four m6A-related lncRNAs. Besides, we also detected five m6A-related lncRNA expression levels in 22 clinical samples using quantitative real-time polymerase chain reaction assay.
Highlights
Gliomas are obstinate intracranial tumors with very poor mortality and recurrence rates (Jiang et al, 2016)
Combined with the prognostic information, univariate Cox regression was implemented to screen m6A-related prognostic lncRNAs from the 75 m6A-related lncRNAs in both the The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets (p < 0.05), respectively
The results revealed that lower-grade glioma (LGG) patients with wildtype isocitrate dehydrogenase (IDH), 1p/19q non-co-deletion status, unmethylated methylguanineDNA methyltransferase (MGMT), older age and World Health Organization (WHO) grade III (Figures 4A–E) had higher risk scores, while the risk score was not associated with gender (Figure 4F)
Summary
Gliomas are obstinate intracranial tumors with very poor mortality and recurrence rates (Jiang et al, 2016). They are extremely difficult to remove by neurosurgical resection due to their invasiveness. Lower-grade gliomas (LGGs) can evolve to higher-grade gliomas and develop resistance to chemotherapy. These factors result in gliomas having a persistently high mortality m6A-Related lncRNAs in LGG rate. Recent research had revealed that m6A modification can regulate oncogenesis and tumor progression in several kinds of cancers, including glioma. Bioinformatic research has revealed that dysregulation of m6A regulators involved in the malignant development of gliomas (Chai et al, 2019)
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