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