Dataset Information

M⁶A regulator-mediated methylation modification patterns and tumor immune microenvironment in sarcoma.

ABSTRACT:

Background

Studies have shown that the RNA N⁶-methyladenosine (m⁶A) modification patterns are extensively involved in the development of multiple tumors. However, the association between the m⁶A regulator expression patterns and the sarcoma tumor immune microenvironment (TIME) remains unclear.

Methods

We systematically evaluated the m⁶A regulator expression patterns in patients with sarcoma based on known 23 m⁶A regulators. Different m⁶A regulator expression patterns were analyzed using gene set variation analysis and a single-sample gene set enrichment analysis algorithm. According to the results of consensus clustering, we classified the patients into four different clusters. Next, we subjected the four clusters to differential genetic analysis and established m⁶A-related differentially expressed genes (DEGs). We then calculated the m⁶A-related DEGs score and constructed the m⁶A-related gene signature, named m⁶A score. Finally, the 259 sarcoma samples were divided into high- and low-m⁶A score groups. We further evaluated the TIME landscape between the high- and low-m⁶A score groups.

Results

We identified four different m⁶A modification clusters and found that each cluster had unique metabolic and immunological characteristics. Based on the 19 prognosis-related DEGs, we calculated the principal component analysis scores for each patient with sarcoma and classified them into high- and low-m⁶A score groups.

Conclusions

The m⁶A regulator expression patterns and complexity of the sarcoma TIME landscape are closely related to each other. Systematic evaluation of m⁶A regulator expression patterns and m⁶A scores in patients with sarcoma will enhance our understanding of TIME characteristics.

SUBMITTER: Li Z

PROVIDER: S-EPMC8791212 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Recent studies have highlighted the biological significance of RNA N6-methyladenosine (m6A) modification in tumorigenicity and progression. However, it remains unclear whether m6A modifications also have potential roles in immune regulation and tumor microenvironment (TME) formation. Methods: In this study, we curated 23 m6A regulators and performed consensus molecular subtyping with NMF algorithm to determine m6A modification patterns and the m6A-related gene signature in colon cancer (CC). The ssGSEA and CIBERSORT algorithms were employed to quantify the relative infiltration levels of various immune cell subsets. An PCA algorithm based m6Sig scoring scheme was used to evaluate the m6A modification patterns of individual tumors with an immune response. Results: Three distinct m6A modification patterns were identified among 1307 CC samples, which were also associated with different clinical outcomes and biological pathways. The TME characterization revealed that the identified m6A patterns were highly consistent with three known immune profiles: immune-inflamed, immune-excluded, and immune-desert, respectively. Based on the m6Sig score, which was extracted from the m6A-related signature genes, CC patients can be divided into high and low score subgroups. Patients with lower m6Sig score was characterized by prolonged survival time and enhanced immune infiltration. Further analysis indicated that lower m6Sig score also correlated with greater tumor mutation loads, PD-L1 expression, and higher mutation rates in SMGs (e.g., PIK3CA and SMAD4). In addition, patients with lower m6Sig scores showed a better immune responses and durable clinical benefits in three independent immunotherapy cohorts. Conclusions: This study highlights that m6A modification is significantly associated with TME diversity and complexity. Quantitatively evaluating the m6A modification patterns of individual tumors will strengthen our understanding of TME characteristics and promote more effective immunotherapy strategies.

Project description:Background: Osteoarthritis is a common chronic degenerative disease, and recently, an increasing number of studies have shown that immunity plays an important role in the progression of osteoarthritis, which is exacerbated by local inflammation. The role of N6-methyladenine (m6A) modification in immunity is being explored. However, the role of m6A modification in regulating the immune microenvironment of osteoarthritis remains unknown. In this study, we sought to discuss the association between the N6-methyladenine (m6A) modification and the immune microenvironment of osteoarthritis. Methods: First, the data and gene expression profiles of 139 samples, including 33 healthy samples and 106 osteoarthritis samples, were obtained from the Genetics osteoARthritis and Progression (GARP) study. Then the differences in m6A regulators between healthy individuals and osteoarthritis patients were analyzed. The correlation between m6A regulators and immune characteristics was also investigated by single-sample gene set enrichment analysis (ssGSEA). Principal component analysis (PCA), Gene Set Variation Analysis (GSVA) enrichment analysis, weighted gene coexpression network analysis (WGCNA), and Associated R packages were used to identify the m6A phenotype and its biological functions. Results: A total of 23 m6A regulators were involved in this study. We found a close correlation between most m6A regulators in all samples as well as in osteoarthritis samples. VIRMA and LRPPRC were the most highly correlated m6A regulators and showed a positive correlation, whereas VIRMA and RBM15B were the most negatively correlated. M6A regulators are associated with osteoarthritis immune characteristics. For example, MDSC cell abundance was strongly correlated with RBM15B and HNRNPC. Meanwhile, RBM15B and HNRNPC were important effectors of natural killer cell immune responses. IGFBP3 is an important regulator of cytolytic activity immune function. We performed an unsupervised consensus cluster analysis of the osteoarthritis samples based on the expression of 23 m6A regulators. Three different m6A subtypes of osteoarthritis were identified, including 27 samples in subtype C1, 21 samples in subtype C2, and 58 samples in subtype C3. Different m6A subtypes have unique biological pathways and play different roles in the immune microenvironment of osteoarthritis. Conclusion: The m6A modification plays a crucial role in the diversity and complexity of the immune microenvironment in osteoarthritis.

Dataset Information

M⁶A regulator-mediated methylation modification patterns and tumor immune microenvironment in sarcoma.

Background

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

M6A regulator-mediated methylation modification patterns and tumor immune microenvironment in sarcoma.

Background

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

M⁶A regulator-mediated methylation modification patterns and tumor immune microenvironment in sarcoma.