Abstract
BackgroundN6-methyladenosine (m6A) RNA methylation and tumor immune microenvironment played crucial roles in cancer development. However, their association in gliomas remains to be fully elucidated.MethodsA total of 2144 glioma patients from CGGA, TCGA, and Rembrandt databases were extracted in our study, in which 325 were set as the training cohort and 1819 were defined as the validation cohort. Survival differences evaluated by Kaplan–Meier analysis between groups. Patients were clustered into subgroups by consensus clustering. ESTIMATE algorithm was applied to calculate immune and stroma scores. The infiltration of immune cells was characterized by TIMER algorithm. The risk signature was constructed by multivariate Cox regression analysis.ResultsNineteen m6A regulators were highly expressed in glioma tissues. The expression of m6A regulators was associated with prognoses, grade, isocitrate dehydrogenase (IDH) status, and 1p19q status of gliomas. Two subgroups were identified by consensus clustering, in which cluster 1 was associated with favorable prognosis, high stroma and immune scores, and high immune infiltration. When the patients were divided into high risk and low risk groups based on their risk scores, we found that patients in the high risk group had poor prognoses. Besides, patients in the high risk group had a higher stroma and immune scores, and higher abundance of immune infiltration. These results were further verified in the validation cohort, which contained three independent datasets. Moreover, patients in the low risk group enjoyed better prognoses without chemoradiotherapy or single chemotherapy.ConclusionOur study revealed that m6A regulators could predict the prognosis and therapeutic efficacy, and were also associated with the immune microenvironment in gliomas.
Highlights
Gliomas are the most common primary malignancies in the central nervous system
A total of 2144 glioma samples were enrolled in our study, in which 325 samples extracted from the Chinese Glioma Genome Atlas (CGGA) database (CGGA325) were defined as the training cohort; 693 samples extracted from the CGGA database (CGGA693), 651 samples extracted from the The Cancer Genome Atlas (TCGA) database, and 475 samples extracted from the Rembrandt database were defined as the validation cohort; 20 normal tissues extracted from the CGGA database were termed as the control group
Results showed that 19 N6-methyladenosine methylation (m6A) regulators were significantly higher in gliomas compared with normal brain tissue (p < 0.05) (Figure 1A); whereas no significant difference was detected between gliomas and normal tissue regarding the expression of METTL16, alkB homolog 5 (ALKBH5), and METTL5 (p > 0.05)
Summary
The morbidity of gliomas is approximately 7 cases per 100,000 people, which accounts for the majority of primary brain tumors (Ostrom et al, 2019). Patients with a higher grade glioma suffer from a worse prognosis. The 10-year survival rate of patients with low-grade glioma is 47% with a median survival time of 11.6 years (Ohgaki and Kleihues, 2005; Smoll et al, 2012). Since patients with gliomas have such a poor prognosis, there is a clear urgent to find novel biomarkers to predict the prognosis. Additional studies are needed to explore novel biomarkers to predict the prognosis of glioma patients. N6-methyladenosine (m6A) RNA methylation and tumor immune microenvironment played crucial roles in cancer development. Their association in gliomas remains to be fully elucidated
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