Dataset Information

RNA m⁵C regulator-mediated modification patterns and the cross-talk between tumor microenvironment infiltration in gastric cancer.

ABSTRACT: The effect of immunotherapy strategy has been affirmed in the treatment of various tumors. Nevertheless, the latent role of RNA 5-methylcytosine (m⁵C) modification in gastric cancer (GC) tumor microenvironment (TME) cell infiltration is still unclear. We systematically explore the m⁵C modification patterns of 2,122 GC patients from GEO and TCGA databases by 16 m⁵C regulators and related these patterns to TME characteristics. LASSO Cox regression was employed to construct the m⁵Cscore based on the expression of regulators and DEGs, which was used to evaluate the prognosis. All the GC patients were divided into three m⁵C modification clusters with distinct gene expression characteristics and TME patterns. GSVA, ssGSEA, and TME cell infiltration analysis showed that m⁵C clusters A, B, and C were classified as immune-desert, immune-inflamed, and immune-excluded phenotype, respectively. The m⁵Cscore system based on the expression of eight genes could effectively predict the prognosis of individual GC patients, with AUC 0.766. Patients with a lower m⁵Cscore were characterized by the activation of immunity and experienced significantly longer PFS and OS. Our study demonstrated the non-negligible role of m⁵C modification in the development of TME complexity and inhomogeneity. Assessing the m⁵C modification pattern for individual GC patients will help recognize the infiltration characterization and guide more effective immunotherapy treatment.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC9646743 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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RNA m5C regulator-mediated modification patterns and the cross-talk between tumor microenvironment infiltration in gastric cancer.

Zhang Qiang Q Sun Xiangfei X Sun Jianyi J Lu Jiangshen J Gao Xiaodong X Shen Kuntang K Qin Xinyu X

Frontiers in immunology 20221027

The effect of immunotherapy strategy has been affirmed in the treatment of various tumors. Nevertheless, the latent role of RNA 5-methylcytosine (m5C) modification in gastric cancer (GC) tumor microenvironment (TME) cell infiltration is still unclear. We systematically explore the m5C modification patterns of 2,122 GC patients from GEO and TCGA databases by 16 m5C regulators and related these patterns to TME characteristics. LASSO Cox regression was employed to c ...[more]

PMID: 36389669

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Project description:BackgroundRecently, many studies have been conducted to examine immune response modification at epigenetic level, but the candidate effect of RNA 5-methylcytosine (m5 C) modification on tumor microenvironment (TME) of acute myeloid leukemia (AML) is still unknown at present.MethodsWe assessed the patterns of m5 C modification among 417 AML cases by using nine m5 C regulators. Thereafter, we associated those identified modification patterns with TME cell infiltration features. Additionally, stepwise regression and LASSO Cox regression analyses were conducted for quantifying patterns of m5 C modification among AML cases to establish the m5 C-score. Meanwhile, we validated the expression of genes in the m5C-score model by qRT-PCR. Finally, the present work analyzed the association between m5 C-score and AML clinical characteristics and prognostic outcomes.ResultsIn total, three different patterns of m5 C modification (m5 C-clusters) were identified, and highly differentiated TME cell infiltration features were also identified. On this basis, evaluating patterns of m5 C modification in single cancer samples was important for evaluating the immune/stromal activities in TME and for predicting prognosis. In addition, the m5 C-score was established, which showed a close relation with the overall survival (OS) of test and training set samples. Moreover, multivariate Cox analysis suggested that our constructed m5 C-score served as the independent predicting factor for the prognosis of AML (hazard ratio = 1.57, 95% confidence interval = 1.38-1.79, p < 1e-5 ).ConclusionsThis study shows that m5 C modification may be one of the key roles in the formation of diversity and complexity of TME. Meanwhile, assessing the patterns of m5 C modification among individual cancer samples is of great importance, which provides insights into cell infiltration features within TME, thereby helping to develop relevant immunotherapy and predict patient prognostic outcomes.

Project description:BackgroundThe role of epigenetic modulation in immunity is receiving increased recognition-particularly in the context of RNA N6-methyladenosine (m6A) modifications. Nevertheless, it is still uncertain whether m6A methylation plays a role in the onset and progression of intracranial aneurysms (IAs). This study aimed to establish the function of m6A RNA methylation in IA, as well as its correlation with the immunological microenvironment.MethodsOur study included a total of 97 samples (64 IA, 33 normal) in the training set and 60 samples (44 IA, 16 normal) in the validation set to systematically assess the pattern of RNA modifications mediated by 22 m6A regulators. The effects of m6A modifications on immune microenvironment features, i.e., immune response gene sets, human leukocyte antigen (HLA) genes, and infiltrating immune cells were explored. We employed Lasso, machine learning, and logistic regression for the purpose of identifying an m6A regulator gene signature of IA with external data validation. For the unsupervised clustering analysis of m6A modification patterns in IA, consensus clustering methods were employed. Enrichment analysis was used to assess immune response activity along with other functional pathways. The identification of m6A methylation markers was identified based on a protein-protein interaction network and weighted gene co-expression network analysis.ResultsWe identified an m6A regulator signature of IGFBP2, IGFBP1, IGF2BP2, YTHDF3, ALKBH5, RBM15B, LRPPRC, and ELAVL1, which could easily distinguish individuals with IA from healthy individuals. Unsupervised clustering revealed three m6A modification patterns. Gene enrichment analysis illustrated that the tight junction, p53 pathway, and NOTCH signaling pathway varied significantly in m6A modifier patterns. In addition, the three m6A modification patterns showed significant differences in m6A regulator expression, immune microenvironment, and bio-functional pathways. Furthermore, macrophages, activated T cells, and other immune cells were strongly correlated with m6A regulators. Eight m6A indicators were discovered-each with a statistically significant correlation with IA-suggesting their potential as prognostic biological markers.ConclusionOur study demonstrates that m6A RNA methylation and the immunological microenvironment are both intricately correlated with the onset and progression of IA. The novel insight into patterns of m6A modification offers a foundation for the development of innovative treatment approaches for IA.

Dataset Information

RNA m⁵C regulator-mediated modification patterns and the cross-talk between tumor microenvironment infiltration in gastric cancer.

Publications

RNA m<sup>5</sup>C regulator-mediated modification patterns and the cross-talk between tumor microenvironment infiltration in gastric cancer.

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