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核心技术专利:CN118964589B侵权必究
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N6-甲基腺苷(m6A)连接的长非编码 RNA 与胶质瘤患者的生存和免疫浸润有关。

N6-methyladenosine (m6A)-connected lncRNAs are linked to survival and immune infiltration in glioma patients.

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Jiangxi Key Laboratory of Neurological Tumors and Cerebrovascular Diseases, Nanchang, China.

出版信息

Biosci Rep. 2023 May 5;43(5). doi: 10.1042/BSR20222100.


DOI:10.1042/BSR20222100
PMID:37083719
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10170299/
Abstract

BACKGROUND: The connection between m6A-assiociateed lncRNAs and prognosis has been demonstrated in multiple types of tumors. However, potential roles of m6A-assiociateed lncRNAs in glioma is still rare. METHODS: We implemented consensus cluster analysis to group the downloaded samples into two subtypes. The least absolute shrinkage and selection operator (LASSO) analysis was used to create a risk model. Additionally, the conjunction between m6A-related lncRNAs and immune cells infiltration was explored by conducting the R package. Ultimately, we inspected the underlying downstream pathways of the two subtypes by performing Gene Set Enrichment Analysis (GSEA). The expression level of m6A-connected lncRNAs in glioma were examined by conducting in vitro experiments. RESULTS: We ascertained two subtypes of glioma in line with the consensus clustering of m6A-associated lncRNAs. We confirmed that age, grade, and IDH are related to the two subtypes. Additionally, the immune cells infiltration and immune checkpoint molecules of the two clusters were discussed. A risk signature including AL359643.3, AL445524.1, AL162231.2, AL117332.1, AP001486.2, POLR2J4, AC120036.4, LINC00641, LINC00900, CRNDE, and AL158212.3, was identified using the Cox regression and LASSO analyses. We also verified the prognostic value and discussed the immune cells infiltration and immune checkpoint molecules of the risk signature. In vitro experiments verified that the m6A-associated lncRNAs was abnormally expressed in glioma. CONCLUSION: We elaborated the significant role of m6A-connected lncRNAs in glioma prognosis and immune infiltration and suggest that these key regulators may serve as underlying therapeutic targets to build up the efficacy of glioma immunotherapy.

摘要

背景:m6A 相关 lncRNA 与多种类型肿瘤的预后之间存在关联。然而,m6A 相关 lncRNA 在神经胶质瘤中的潜在作用仍然很少见。

方法:我们进行了共识聚类分析,将下载的样本分为两个亚型。最小绝对收缩和选择算子(LASSO)分析用于创建风险模型。此外,通过 R 包探索了 m6A 相关 lncRNA 与免疫细胞浸润的关联。最终,通过基因集富集分析(GSEA)检查了两个亚型的潜在下游途径。通过体外实验检测了 m6A 相关 lncRNA 在神经胶质瘤中的表达水平。

结果:我们根据 m6A 相关 lncRNA 的共识聚类确定了两种神经胶质瘤亚型。我们证实年龄、分级和 IDH 与这两种亚型有关。此外,讨论了两个聚类的免疫细胞浸润和免疫检查点分子。使用 Cox 回归和 LASSO 分析,确定了包括 AL359643.3、AL445524.1、AL162231.2、AL117332.1、AP001486.2、POLR2J4、AC120036.4、LINC00641、LINC00900、CRNDE 和 AL158212.3 在内的风险标志物。我们还验证了风险标志物的预后价值,并讨论了免疫细胞浸润和免疫检查点分子。体外实验验证了 m6A 相关 lncRNA 在神经胶质瘤中异常表达。

结论:我们详细阐述了 m6A 相关 lncRNA 在神经胶质瘤预后和免疫浸润中的重要作用,并提出这些关键调节因子可能作为潜在的治疗靶点,提高神经胶质瘤免疫治疗的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/b8336ef77717/bsr-43-bsr20222100-g9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/1e12c687b29c/bsr-43-bsr20222100-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/46d0f19282f9/bsr-43-bsr20222100-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/ff911d96d532/bsr-43-bsr20222100-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/99934c74b024/bsr-43-bsr20222100-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/f897c020a490/bsr-43-bsr20222100-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/c27af5bdb77c/bsr-43-bsr20222100-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/a16de919fd57/bsr-43-bsr20222100-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/36dfcbb49429/bsr-43-bsr20222100-g8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/b8336ef77717/bsr-43-bsr20222100-g9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/1e12c687b29c/bsr-43-bsr20222100-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/46d0f19282f9/bsr-43-bsr20222100-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/ff911d96d532/bsr-43-bsr20222100-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/99934c74b024/bsr-43-bsr20222100-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/f897c020a490/bsr-43-bsr20222100-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/c27af5bdb77c/bsr-43-bsr20222100-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/a16de919fd57/bsr-43-bsr20222100-g7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/36dfcbb49429/bsr-43-bsr20222100-g8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f9/10170299/b8336ef77717/bsr-43-bsr20222100-g9.jpg

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[1]
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引用本文的文献

[1]
Characterization of lysine crotonylation-related lncRNAs for prognostic assessment and immune response in glioma.

Front Pharmacol. 2025-6-30

[2]
Epitranscriptomic analysis reveals clinical and molecular signatures in glioblastoma.

Acta Neuropathol Commun. 2025-4-11

[3]
Systematic transcriptomic analysis of childhood medulloblastoma identifies N6- methyladenosine-dependent lncRNA signatures associated with molecular subtype, immune cell inltration, and prognosis.

Res Sq. 2024-9-2

[4]
Systematic transcriptomic analysis of childhood medulloblastoma identifies N6-methyladenosine-dependent lncRNA signatures associated with molecular subtype, immune cell infiltration, and prognosis.

Acta Neuropathol Commun. 2024-8-28

本文引用的文献

[1]
Interaction between m6A methylation and noncoding RNA in glioma.

Cell Death Discov. 2022-6-10

[2]
Construction of a Novel Signature and Prediction of the Immune Landscape in Soft Tissue Sarcomas Based on N6-Methylandenosine-Related LncRNAs.

Front Mol Biosci. 2021-10-15

[3]
Prognostic Value of N6-Methyladenosine-Related lncRNAs in Early-Stage Colorectal Cancer: Association With Immune Cell Infiltration and Chemotherapeutic Drug Sensitivity.

Front Mol Biosci. 2021-10-12

[4]
Prognostic Signature of Hepatocellular Carcinoma and Analysis of Immune Infiltration Based on m6A-Related lncRNAs.

Front Oncol. 2021-8-30

[5]
Immune Infiltrates of mA RNA Methylation-Related lncRNAs and Identification of PD-L1 in Patients With Primary Head and Neck Squamous Cell Carcinoma.

Front Cell Dev Biol. 2021-6-4

[6]
Comprehensive analysis of N6-methyladenosine -related long non-coding RNAs and immune cell infiltration in hepatocellular carcinoma.

Bioengineered. 2021-12

[7]
METTL3 enhances the stability of MALAT1 with the assistance of HuR via m6A modification and activates NF-κB to promote the malignant progression of IDH-wildtype glioma.

Cancer Lett. 2021-7-28

[8]
Analysis of m6A-Related Signatures in the Tumor Immune Microenvironment and Identification of Clinical Prognostic Regulators in Adrenocortical Carcinoma.

Front Immunol. 2021

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