Dataset Information

M⁵C Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Papillary Thyroid Carcinoma.

ABSTRACT: Recently, immune response modulation at the epigenetic level is illustrated in studies, but the possible function of RNA 5-methylcytosine (m⁵C) modification in cell infiltration within the tumor microenvironment (TME) is still unclear. Three different m⁵C modification patterns were identified, and high differentiation degree was observed in the cell infiltration features within TME under the above three identified patterns. A low m⁵C-score, which was reflected in the activated immunity, predicted the relatively favorable prognostic outcome. A small amount of effective immune infiltration was seen in the high m⁵C-score subtype, indicating the dismal patient survival. Our study constructed a diagnostic model using the 10 signature genes highly related to the m⁵C-score, discovered that the model exhibited high diagnostic accuracy for PTC, and screened out five potential drugs for PTC based on this m5C-score model. m⁵C modification exerts an important part in forming the TME complexity and diversity. It is valuable to evaluate the m⁵C modification patterns in single tumors, so as to enhance our understanding towards the infiltration characterization in TME.

SUBMITTER: Li F

PROVIDER: S-EPMC8597900 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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m5C Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Papillary Thyroid Carcinoma.

Li Fei F Deng Qingmei Q Pang Xiaoxi X Huang Shan S Zhang Jingmiao J Zhu Xiaxia X Chen Hong H Liu Xiuxia X

Frontiers in oncology 20211103

Recently, immune response modulation at the epigenetic level is illustrated in studies, but the possible function of RNA 5-methylcytosine (m5C) modification in cell infiltration within the tumor microenvironment (TME) is still unclear. Three different m5C modification patterns were identified, and high differentiation degree was observed in the cell infiltration features within TME under the above three identified patterns. A low m5C-score, which was reflected in ...[more]

PMID: 34804923

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Project description:Background: 5-Methylcytosine (m5C) plays essential roles in hepatocellular carcinoma (HCC), but the association between m5C regulation and immune cell infiltration in HCC has not yet been clarified. Methods: In this study, we analysed 371 patients with HCC from The Cancer Genome Atlas (TCGA) database, and the expression of 13 m5C regulators was investigated. Additionally, gene set variation analysis (GSVA), unsupervised clustering analysis, single-sample gene set enrichment analysis (ssGSEA), correlation analysis, and immunohistochemical (IHC) staining were performed. Results: Among the 371 patients, 41 had mutations in m5C regulators, the frequency of which was 11.26%. Compared with normal hepatic tissues, the expression of m5C regulators with copy number variations (CNVs) expansion was significantly higher than that in HCC tissues. Then, we identified three m5C modification patterns that had obvious tumour microenvironment (TME) cell infiltration characteristics. The prognostic analysis of the three major m5C modification subtypes showed that Cluster-2 had a clear survival advantage over the others. In addition, we found that DNMT1 was highly expressed in tumour tissues compared with normal tissues in a tissue microarray (TMA) and that it was positively correlated with many TME-infiltrating immune cells. High expression of the m5C regulator DNMT1 was related to a poor prognosis in patients with HCC. Furthermore, we developed three distinct Immu-clusters. Importantly, mRNAs related to the transcription of growth factor β (TGF-β)/EMT pathway were significantly up-regulated in Immu-cluster 2, indicating that this cluster is considered to be the immune rejection phenotype. Immu-cluster 3 showed elevated expression of mRNAs related to immune checkpoint genes. Conclusion: Our work revealed the association between m5C modification and immune regulators in the TME. These findings also suggest that DNMT1 has great potential as a prognostic biomarker and therapeutic target for HCC.

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.

Dataset Information

M⁵C Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Papillary Thyroid Carcinoma.

Publications

m<sup>5</sup>C Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Papillary Thyroid Carcinoma.

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Dataset Information

M5C Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Papillary Thyroid Carcinoma.

Publications

m<sup>5</sup>C Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Papillary Thyroid Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

M⁵C Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Papillary Thyroid Carcinoma.