m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer

Zhang, Bo; Wu, Qiong; Li, Ben; Wang, Defeng; Wang, Lei; Zhou, You

doi:10.1186/s12943-020-01170-0

Cited by 718 publications

(717 citation statements)

References 51 publications

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“…In the gastric tumors, m6A modification patterns could predict the stages of tumor inflammation, TME stromal activity, genetic variation and patient prognosis. Lower m6A score indicated an inflamed TME phenotype and enhanced response to anti-PD-1/L1 immunotherapy ( 21 ). The high expression of WTAP, a m6A methyltransferase, was also associated with RNA methylation and its low expression was related to a high T cell-related immune response in gastric cancer ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

Prognosis Analysis and Validation of m6A Signature and Tumor Immune Microenvironment in Glioma

Lin

Zhang

et al. 2020

Front. Oncol.

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Glioma is one of the most typical intracranial tumors, comprising about 80% of all brain malignancies. Several key molecular signatures have emerged as prognostic biomarkers, which indicate room for improvement in the current approach to glioma classification. In order to construct a more veracious prediction model and identify the potential prognosis-biomarker, we explore the differential expressed m 6 A RNA methylation regulators in 665 gliomas from TCGA-GBM and TCGA-LGG. Consensus clustering was applied to the m6A RNA methylation regulators, and two glioma subgroups were identified with a poorer prognosis and a higher grade of WHO classification in cluster 1. The further chi-squared test indicated that the immune infiltration was significantly enriched in cluster 1, indicating a close relation between m 6 A regulators and immune infiltration. In order to explore the potential biomarkers, the weighted gene co-expression network analysis (WGCNA), along with Least absolute shrinkage and selection operator (LASSO), between high/low immune infiltration and m 6 A cluster 1/2 groups were utilized for the hub genes, and four genes ( TAGLN2, PDPN, TIMP1, EMP3) were identified as prognostic biomarkers. Besides, a prognostic model was constructed based on the four genes with a good prediction and applicability for the overall survival (OS) of glioma patients (the area under the curve of ROC achieved 0.80 (0.76–0.83) and 0.72 (0.68–0.76) in TCGA and Chinese Glioma Genome Atlas (CGGA), respectively). Moreover, we also found PDPN and TIMP1 were highly expressed in high-grade glioma from The Human Protein Atlas database and both of them were correlated with m6A and immune cell marker in glioma tissue samples. In conclusion, we construct a novel prognostic model which provides new insights into glioma prognosis. The PDPN and TIMP1 may serve as potential biomarkers for prognosis of glioma.

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Section: Introductionmentioning

confidence: 99%

Prognosis Analysis and Validation of m6A Signature and Tumor Immune Microenvironment in Glioma

Lin

Zhang

et al. 2020

Front. Oncol.

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“…Previously, several studies have investigated some m 6 A or expression patterns of m 6 A-related genes in GC. Zhang et al evaluated the m 6 A modification patterns of GC samples based on 21 m 6 A regulators and their correlation with tumor microenvironmental (TME) cell infiltration [ 9 ]. Another research conducted by Guan et al analyzed the expression status and determinate prognostic values of m 6 A-related genes in GC [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Joint analysis of lncRNA m6A methylome and lncRNA/mRNA expression profiles in gastric cancer

Sun

et al. 2020

Cancer Cell Int

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Background N6-methyladenosine (m6A) modification might be closely associated with the genesis and development of gastric cancer (GC). Currently, the evidence established by high-throughput assay for GC-related m6A patterns based on long non-coding RNAs (lncRNAs) remains limited. Here, a joint analysis of lncRNA m6A methylome and lncRNA/mRNA expression profiles in GC was performed to explore the regulatory roles of m6A modification in lncRNAs. Methods Three subjects with primary GC were enrolled in our study and paired sample was randomly selected from GC tissue and adjacent normal tissue for each case. Methylated RNA Immunoprecipitation NextGeneration Sequencing (MeRIP-Seq) and Microarray Gene Expression Profiling was subsequently performed. Then co-expression analysis and gene enrichment analysis were successively conducted. Results After data analysis, we identified 191 differentially m6A-methylated lncRNAs, 240 differentially expressed lncRNAs and 229 differentially expressed mRNAs in GC. Furthermore, four differentially m6A-methylated and expressed lncRNAs (dme-lncRNAs) were discovered including RASAL2-AS1, LINC00910, SNHG7 and LINC01105. Their potential target genes were explored by co-expression analysis. And gene enrichment analysis suggested that they might influence the cellular processes and biological behaviors involved in mitosis and cell cycle. The potential impacts of these targets on GC cells were further validated by CCLE database and literature review. Conclusions Four novel dme-lncRNAs were identified in GC, which might exert regulatory roles on GC cell proliferation. The present study would provide clues for the lncRNA m6A methylation-based research on GC epigenetic etiology and pathogenesis.

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“…between the genetic alterations of m 6 A regulatory genes and TP53 pathway in the processing of acute myeloid leukemia (9). Recently, research into the gastric carcinoma proved that m 6 A modification in cancer tissue had a close relationship with tumor microenvironment (10). Certain single-nucleotide polymorphisms (SNPs) in m 6 A modification genes were also proved to have correlation with the formation of CRC (11).…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic Gene Expression Regulation Through m6A Methylation Predicts Prognosis in Stage III Colorectal Cancer

Zhou

et al. 2020

Front. Oncol.

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Background: Methylation of N6 adenosine (m 6 A) plays important regulatory roles in diverse biological processes. The purpose of this research was to explore the potential mechanism of m 6 A modification level on the clinical outcome of stage III colorectal cancer (CRC). Methods: Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were adopted to reveal the signal pathway which was most likely affected by m 6 A methylation. The linear models for microarray data (LIMMA) method and the least absolute shrinkage and selection operator (LASSO) Cox regression model were used to identify the signature. The signature can sensitively separate the patients into high and low risk indicating the relapse-free survival (RFS) time based on time-dependent receiver operating characteristic (ROC) analysis. Then, the multi-gene signature was validated in GSE14333 and the Cancer Genome Atlas (TCGA) cohort. The number of the samples in GSE14333 and TCGA cohort are 63 and 150. Finally, two nomograms were set up and validated to predict prognosis of patients with stage III CRC. Results: The hematopoietic cell lineage (HCL) signaling pathway was disclosed through GSEA and GSVA. Seven HCL-related genes were determined in the LASSO model to construct signature, with AUC 0.663, 0.708, and 0.703 at 1-, 3-, and 5-year RFS, respectively. Independent datasets analysis and stratification analysis indicated that the HCL-related signature was reliable in distinguishing high-and low-risk stage III CRC patients. Two nomograms incorporating the signature and pathological N stage were set up, which yielded good discrimination and calibration in the predictions of prognosis for stage III CRC patients. Conclusions: A novel HCL-related signature was developed as a predictive model for survival rate of stage III CRC patients. Nomograms based on the signature were advantageous to facilitate personalized counseling and treatment in stage III CRC.

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m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer

Cited by 718 publications

References 51 publications

Prognosis Analysis and Validation of m6A Signature and Tumor Immune Microenvironment in Glioma

Prognosis Analysis and Validation of m6A Signature and Tumor Immune Microenvironment in Glioma

Joint analysis of lncRNA m6A methylome and lncRNA/mRNA expression profiles in gastric cancer

Hematopoietic Gene Expression Regulation Through m6A Methylation Predicts Prognosis in Stage III Colorectal Cancer

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