Dataset Information

RNA N6-Methyladenosine Regulator-Mediated Methylation Modifications Pattern and Immune Infiltration Features in Glioblastoma.

ABSTRACT: Glioblastoma (GBM) is a group of intracranial neoplasms with intra-tumoral heterogeneity. RNA N6-methyladenosine (m⁶A) methylation modification reportedly plays roles in immune response. The relationship between the m⁶A modification pattern and immune cell infiltration in GBM remains unknown. Utilizing expression data of GBM patients, we thoroughly explored the potential m⁶A modification pattern and m⁶A-related signatures based on 21 regulators. Thereafter, the m⁶A methylation modification-based prognostic assessment pipeline (MPAP) was constructed to quantitatively assess GBM patients' clinical prognosis combining the Robustness and LASSO regression. Single-sample gene-set enrichment analysis (ssGSEA) was used to estimate the specific immune cell infiltration level. We identified two diverse clusters with diverse m⁶A modification characteristics. Based on differentially expressed genes (DEGs) within two clusters, m⁶A-related signatures were identified to establish the MPAP, which can be used to quantitatively forecast the prognosis of GBM patients. In addition, the relationship between 21 m⁶A regulators and specific immune cell infiltration was demonstrated in our study and the m⁶A regulator ELAVL1 was determined to play an important role in the anticancer response to PD-L1 therapy. Our findings indicated the relationship between m⁶A methylation modification patterns and tumor microenvironment immune cell infiltration, through which we could comprehensively understand resistance to multiple therapies in GBM, as well as accomplish precise risk stratification according to m⁶A-related signatures.

SUBMITTER: Pan Y

PROVIDER: S-EPMC7947873 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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RNA N6-Methyladenosine Regulator-Mediated Methylation Modifications Pattern and Immune Infiltration Features in Glioblastoma.

Pan Yimin Y Xiao Kai K Li Yue Y Li Yuzhe Y Liu Qing Q

Frontiers in oncology 20210225

Glioblastoma (GBM) is a group of intracranial neoplasms with intra-tumoral heterogeneity. RNA N6-methyladenosine (m6A) methylation modification reportedly plays roles in immune response. The relationship between the m6A modification pattern and immune cell infiltration in GBM remains unknown. Utilizing expression data of GBM patients, we thoroughly explored the potential m6A modification pattern and m6A-related signatures based on 21 regulators. Therea ...[more]

PMID: 33718217

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Project description:BackgroundSeveral studies have revealed that N6-methyladenosine (m6A) regulation is involved in various biological processes and cancer progression. Nevertheless, the potential effects of m6A modifications in the tumor immune microenvironment (TIME) and on immune regulation in pancreatic adenocarcinoma (PAAD) remains unclear.MethodsA consensus clustering algorithm was used to identify different m6A modification patterns and construct an m6A-associated gene signature based on 23 m6A regulators in PAAD. The CIBERSORT and ssGSEA algorithms were used to estimate the components of the immune cells in each sample. The PCA algorithm was used to develop the m6Ascore system for the evaluation of m6A modification patterns in each sample.ResultsTwo m6A modification patterns with different biological properties and prognoses were identified in 176 PAAD patient samples. The features of TIME between the two patterns were similar, with two definite immune phenotypes: immune-inflamed and immune-excluded. Based on the m6A phenotype-associated signature genes, we constructed an m6Ascore system to investigate the m6A modification pattern of each sample, profile the dissection of physiological processes, immune infiltration, clinical prognosis, immunotherapy, and genetic variation. Patients with low m6Ascore scores had better clinical outcomes, enhanced immune infiltration, and lower expression of immunotherapeutic drug targets, such as CD274 and PDCD1LG2. Further research indicated that the m6Ascore and tumor mutation burden were significantly correlated, and patients with low m6Ascore had higher mutation rates in SMAD4 and TTN. Moreover, TNFRSF21 was significantly upregulated in PAAD tumor tissues and cell lines. Lower expression of TNFRSF21 had a prominent advantage in survival and was correlated with a low level of immune infiltration. PAAD samples with different TNFRSF21 expression levels showed significantly distinct sensitivities to chemotherapeutic agents.ConclusionsThis study revealed that m6A modification patterns could play an important role in the diversity and complexity of TIME, and the m6Ascore system could serve as an independent and powerful prognostic biomarker and is latently related to PAAD immunotherapies. Quantitative determination of m6A modification patterns in individual patients will be instrumental in mapping the TIME landscape and further optimizing precision immunotherapy.

Dataset Information

RNA N6-Methyladenosine Regulator-Mediated Methylation Modifications Pattern and Immune Infiltration Features in Glioblastoma.

Publications

RNA N6-Methyladenosine Regulator-Mediated Methylation Modifications Pattern and Immune Infiltration Features in Glioblastoma.

Similar Datasets

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