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rmscore, writers, rna, hcc, fig, methylation, article, analysis, cancer, modification, patients, google, scholar, immune, expression, cell, table, cluster, high, survival, cas, nsun, additional, tumor, cohort, file, carcinoma, low, hepatocellular, correlation, drug, mutation, clinical, cohorts, liver, mettl, sensitivity, degs, model, pathways, zhang, infiltration, response, immunotherapy, signaling, group, gene, clustering, tme, potential,

Topics {✒️}

cbx3-mediated c-met/akt/mtor axis sum {pc}_{1}+\sum {pc}_{2} hur-ets1-p21/p27 axis m6a-hur-dependent epigenetic silencing account european journal mir-522–3p/socs5 axis generate mrna–mirna–lncrna network pi3k/akt/mtor signaling ube2c-mediated p53 ubiquitination cancer genome atlas kaplan–meier curves demonstrating kaplan–meier curves show activating akt/mtor signaling pi3k/mtor signaling pathway rna methylation-based classifier rm_patterns-based risk model 2′-o-methylation writer fibrillarin fast-growing hepatocellular carcinomas rna methylation-based model anti-pd-l1 blockers crucial post-translational modification interferon α/γ response rna methylation-related genes rm writers-related signature including includes n1-methyladenosine european economic area multi-center clinical cohorts pd-l1 blockade immunotherapy metastatic urothelial carcinoma rna modification profile anti-pd-l1 treatment mirna–mrna interactions overlapped privacy choices/manage cookies bmc bioinformatics rm writer signature rm phenotype-related degs forecast tumor microenvironment a-related gene expression authors scientific editing univariate cox analysis foxo3-mediated autophagy rna methylation phenotype conducted gsva enrichment analysis protein–rna interactions [5 rna methylation modifications post-translational modification rna methylation modification kaplan–meier method rna methylation model rna methylated modification

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         headline:Integrated investigation of the clinical implications and targeted landscape for RNA methylation modifications in hepatocellular carcinoma
         description:RNA methylation (RM) is a crucial post-translational modification (PTM) that directs epigenetic regulation. It mostly consists of N1-methyladenosine (m1A), 5-methylcytosine (m5C), N3-methylcytidine (m3C), N6-methyladenosine (m6A), and 2′-O-methylation (Nm). The “writers” mainly act as intermediaries between these modifications and associated biological processes. However, little is known about the interactions and potential functions of these RM writers in hepatocellular carcinoma (HCC). The expression properties and genetic alterations of 38 RM writers were assessed in HCC samples from five bioinformatic datasets. Two patterns associated with RM writers were identified using consensus clustering. Then, utilizing differentially expressed genes (DEGs) from different RM subtypes, we built a risk model called RM_Score. Additionally, we investigated the correlation of RM_Score with clinical characteristics, tumor microenvironment (TME) infiltration, molecular subtypes, therapeutic response, immunotherapy effectiveness, and competing endogenous RNA (ceRNA) network. RM writers were correlated with TME cell infiltration and prognosis. Cluster_1/2 and gene.cluster_A/B were shown to be capable of distinguishing the HCC patients with poor prognosis after consensus and unsupervised clustering of RNA methylation writers. Additionally, we constructed RNA modification pattern-specific risk model and subdivided the cases into RM_Score high and RM_Score low subgroups. In individual cohorts or merged datasets, the high RM_Score was related to a worse overall survival of HCC patients. RM_Score also exhibited correlations with immune and proliferation related pathways. In response to anti-cancer treatments, the RM_Score had a negative correlation (drug sensitive) with drugs that focused on the MAPK/ERK and metabolism signaling, and a positive correlation (drug resistant) with compounds targeting RKT and PI3K/mTOR signaling pathway. Notably, the RM_Score was connected to the therapeutic effectiveness of PD-L1 blockage, implying that RM writers may be the target of immunotherapy to optimize clinical outcomes. Additionally, a ceRNA network was generated including 2 lncRNAs, 4 miRNAs, and 7 mRNAs that was connected to RM writers. We thoroughly investigated the potential functions of RNA methylation writers and established an RM_patterns-based risk model for HCC patients. This study emphasized the critical functions of RM modification in TME infiltration, targeted therapy, and immunotherapy, providing potential targets for HCC.
         datePublished:2023-01-27T00:00:00Z
         dateModified:2023-01-27T00:00:00Z
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            RNA methylation
            Writer
            Hepatocellular carcinoma
            Tumor microenvironment
            RM_Score
            Drug sensitivity
            Immunotherapy
            Medicine/Public Health
            general
            Infectious Diseases
            Internal Medicine
            Surgery
            Oncology
            Biomedicine
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                     name:Affiliated Hospital of Nanjing University Medical School
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      headline:Integrated investigation of the clinical implications and targeted landscape for RNA methylation modifications in hepatocellular carcinoma
      description:RNA methylation (RM) is a crucial post-translational modification (PTM) that directs epigenetic regulation. It mostly consists of N1-methyladenosine (m1A), 5-methylcytosine (m5C), N3-methylcytidine (m3C), N6-methyladenosine (m6A), and 2′-O-methylation (Nm). The “writers” mainly act as intermediaries between these modifications and associated biological processes. However, little is known about the interactions and potential functions of these RM writers in hepatocellular carcinoma (HCC). The expression properties and genetic alterations of 38 RM writers were assessed in HCC samples from five bioinformatic datasets. Two patterns associated with RM writers were identified using consensus clustering. Then, utilizing differentially expressed genes (DEGs) from different RM subtypes, we built a risk model called RM_Score. Additionally, we investigated the correlation of RM_Score with clinical characteristics, tumor microenvironment (TME) infiltration, molecular subtypes, therapeutic response, immunotherapy effectiveness, and competing endogenous RNA (ceRNA) network. RM writers were correlated with TME cell infiltration and prognosis. Cluster_1/2 and gene.cluster_A/B were shown to be capable of distinguishing the HCC patients with poor prognosis after consensus and unsupervised clustering of RNA methylation writers. Additionally, we constructed RNA modification pattern-specific risk model and subdivided the cases into RM_Score high and RM_Score low subgroups. In individual cohorts or merged datasets, the high RM_Score was related to a worse overall survival of HCC patients. RM_Score also exhibited correlations with immune and proliferation related pathways. In response to anti-cancer treatments, the RM_Score had a negative correlation (drug sensitive) with drugs that focused on the MAPK/ERK and metabolism signaling, and a positive correlation (drug resistant) with compounds targeting RKT and PI3K/mTOR signaling pathway. Notably, the RM_Score was connected to the therapeutic effectiveness of PD-L1 blockage, implying that RM writers may be the target of immunotherapy to optimize clinical outcomes. Additionally, a ceRNA network was generated including 2 lncRNAs, 4 miRNAs, and 7 mRNAs that was connected to RM writers. We thoroughly investigated the potential functions of RNA methylation writers and established an RM_patterns-based risk model for HCC patients. This study emphasized the critical functions of RM modification in TME infiltration, targeted therapy, and immunotherapy, providing potential targets for HCC.
      datePublished:2023-01-27T00:00:00Z
      dateModified:2023-01-27T00:00:00Z
      pageStart:1
      pageEnd:15
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s40001-023-01016-7
      keywords:
         RNA methylation
         Writer
         Hepatocellular carcinoma
         Tumor microenvironment
         RM_Score
         Drug sensitivity
         Immunotherapy
         Medicine/Public Health
         general
         Infectious Diseases
         Internal Medicine
         Surgery
         Oncology
         Biomedicine
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      author:
            name:Jianping Zhang
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                  name:Medical School of Nantong University
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                     type:PostalAddress
                  type:Organization
                  name:Affiliated Hospital of Nanjing University Medical School
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                     type:PostalAddress
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            name:Jie Gao
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                     name:Department of Oncology, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng, China
                     type:PostalAddress
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                     name:Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
                     type:PostalAddress
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                     type:PostalAddress
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            name:Shiyu Xu
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                     name:Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
                     type:PostalAddress
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                  address:
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                     type:PostalAddress
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                  name:Medical School of Nantong University
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                     name:Department of Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
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                  name:Medical School of Nantong University
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      name:Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
      name:Department of Oncology, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng, China
      name:Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
      name:Department of Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
      name:Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
      name:Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
      name:Department of Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
      name:Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
      name:Department of Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China
      name:Department of Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China

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