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泛癌种长链非编码 RNA 特征分析 EMT 与肿瘤免疫的串扰,鉴定出不同的临床结局和对免疫治疗的潜在影响。

Pan-sarcoma characterization of lncRNAs in the crosstalk of EMT and tumour immunity identifies distinct clinical outcomes and potential implications for immunotherapy.

机构信息

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Institute of Haematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

出版信息

Cell Mol Life Sci. 2022 Jul 16;79(8):427. doi: 10.1007/s00018-022-04462-4.


DOI:10.1007/s00018-022-04462-4
PMID:35842562
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11071722/
Abstract

The epithelial-to-mesenchymal transition (EMT) is a reversible process that may interact with tumour immunity through multiple approaches. There is increasing evidence demonstrating the interconnections among EMT-related processes, the tumour microenvironment, and immune activity, as well as its potential influence on the immunotherapy response. Long non-coding RNAs (lncRNAs) are emerging as critical modulators of gene expression. They play fundamental roles in tumour immunity and act as promising biomarkers of immunotherapy response. However, the potential roles of lncRNA in the crosstalk of EMT and tumour immunity are still unclear in sarcoma. We obtained multi-omics profiling of 1440 pan-sarcoma patients from 19 datasets. Through an unsupervised consensus clustering approach, we categorised EMT molecular subtypes. We subsequently identified 26 EMT molecular subtype and tumour immune-related lncRNAs (EILncRNA) across pan-sarcoma types and developed an EILncRNA signature-based weighted scoring model (EILncSig). The EILncSig exhibited favourable performance in predicting the prognosis of sarcoma, and a high-EILncSig was associated with exclusive tumour microenvironment (TME) characteristics with desert-like infiltration of immune cells. Multiple altered pathways, somatically-mutated genes and recurrent CNV regions associated with EILncSig were identified. Notably, the EILncSig was associated with the efficacy of immune checkpoint inhibition (ICI) therapy. Using a computational drug-genomic approach, we identified compounds, such as Irinotecan that may have the potential to convert the EILncSig phenotype. By integrative analysis on multi-omics profiling, our findings provide a comprehensive resource for understanding the functional role of lncRNA-mediated immune regulation in sarcomas, which may advance the understanding of tumour immune response and the development of lncRNA-based immunotherapeutic strategies for sarcoma.

摘要

上皮-间充质转化(EMT)是一个可逆的过程,它可能通过多种途径与肿瘤免疫相互作用。越来越多的证据表明 EMT 相关过程、肿瘤微环境和免疫活性之间存在相互联系,以及它对免疫治疗反应的潜在影响。长链非编码 RNA(lncRNA)正在成为基因表达的关键调控因子。它们在肿瘤免疫中发挥着重要作用,并作为免疫治疗反应的有前途的生物标志物。然而,lncRNA 在 EMT 与肿瘤免疫的串扰中的潜在作用在肉瘤中仍不清楚。我们从 19 个数据集获得了 1440 名泛肉瘤患者的多组学图谱。通过无监督共识聚类方法,我们对 EMT 分子亚型进行了分类。随后,我们在泛肉瘤类型中鉴定了 26 个 EMT 分子亚型和肿瘤免疫相关 lncRNA(EILncRNA),并开发了基于 EILncRNA 特征的加权评分模型(EILncSig)。EILncSig 在预测肉瘤预后方面表现出良好的性能,高 EILncSig 与独特的肿瘤微环境(TME)特征相关,免疫细胞呈沙漠样浸润。确定了与 EILncSig 相关的多个改变的途径、体细胞突变基因和复发性 CNV 区域。值得注意的是,EILncSig 与免疫检查点抑制(ICI)治疗的疗效相关。通过计算药物基因组学方法,我们鉴定了伊立替康等化合物,这些化合物可能具有转化 EILncSig 表型的潜力。通过对多组学图谱的综合分析,我们的研究结果为理解 lncRNA 介导的免疫调节在肉瘤中的功能作用提供了全面的资源,这可能有助于深入了解肿瘤免疫反应,并为肉瘤的 lncRNA 为基础的免疫治疗策略的发展提供依据。

相似文献

[1]
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[7]
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[8]
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引用本文的文献

[1]
Two-step consensus clustering approach to immune cell infiltration: An integrated exploration and validation of prognostic and immune implications in sarcomas.

Heliyon. 2024-10-1

[2]
Integrating bulk-RNA sequencing and single-cell sequencing analyses to characterize adenosine-enriched tumor microenvironment landscape and develop an adenosine-related prognostic signature predicting immunotherapy in lung adenocarcinoma.

Funct Integr Genomics. 2024-1-24

[3]
SPOCK1, as a potential prognostic and therapeutic biomarker for lung adenocarcinoma, is associated with epithelial-mesenchymal transition and immune evasion.

J Transl Med. 2023-12-12

本文引用的文献

[1]
Transcriptional and post-transcriptional control of epithelial-mesenchymal plasticity: why so many regulators?

Cell Mol Life Sci. 2022-3-12

[2]
Mechanisms of Functional Pleiotropy of p73 in Cancer and Beyond.

Front Cell Dev Biol. 2021-9-28

[3]
High Levels of LINC01140 Expression Predict a Good Prognosis and Improve Radiotherapy in Sarcoma Patients.

Crit Rev Eukaryot Gene Expr. 2021

[4]
Noncoding RNAs in tumor metastasis: molecular and clinical perspectives.

Cell Mol Life Sci. 2021-11

[5]
LINC01140 promotes the progression and tumor immune escape in lung cancer by sponging multiple microRNAs.

J Immunother Cancer. 2021-8

[6]
Overexpression of Long Non-Coding RNA MIR22HG Represses Proliferation and Enhances Apoptosis via miR-629-5p/TET3 Axis in Osteosarcoma Cells.

J Microbiol Biotechnol. 2021-10-28

[7]
Fibroblast growth factor receptor 3 alterations and response to immune checkpoint inhibition in metastatic urothelial cancer: a real world experience.

Br J Cancer. 2021-10

[8]
Molecular mechanisms underpinning sarcomas and implications for current and future therapy.

Signal Transduct Target Ther. 2021-6-30

[9]
Epithelial-Mesenchymal Transition Gene Signature Related to Prognostic in Colon Adenocarcinoma.

J Pers Med. 2021-5-26

[10]
Conserved pan-cancer microenvironment subtypes predict response to immunotherapy.

Cancer Cell. 2021-6-14

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