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与铜死亡相关的长链非编码RNA可辨别肉瘤患者的预后和免疫微环境。

Cuproptosis-associated lncRNAs discern prognosis and immune microenvironment in sarcoma victims.

作者信息

Chu Binxiang, Zheng Haihong, Zheng Xiaohe, Feng Xingbing, Hong Zhenghua

机构信息

Department of Orthopedic, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.

Department of Pathology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.

出版信息

Front Cell Dev Biol. 2022 Dec 16;10:989882. doi: 10.3389/fcell.2022.989882. eCollection 2022.

Abstract

Cuproptosis is a fresh form of the copper-elesclomol-triggered, mitochondrial tricarboxylic acid (TCA) dependent cell death. Yet, the subsumed mechanism of cuproptosis-associated lncRNAs in carcinoma is not wholly clarified. Here, We appraised 580 cuproptosis-associated lncRNAs in sarcoma and thereafter construed a module composing of 6 cuproptosis lncRNAs, entitled CuLncScore, utilizing a machine learning methodology. It could outstandingly discern the prognosis of patients in parallel with discriminating tumor immune microenvironment traits. Moreover, we simulate the classification system of cuproptosis lncRNAs by unsupervised learning method to facilitate differentiation of clinical denouement and immunotherapy modality options. Notably, Our Taizhou cohort validated the stability of CuLncScore and the classification system. Taking a step further, we checked these 6 cuproptosis lncRNAs by Quantitative real-time polymerase chain reaction (qRT-PCR) to ascertain their authenticity. All told, our investigations highlight that cuproptosis lncRNAs are involved in various components of sarcoma and assist in the formation of the tumor immune microenvironment. These results provide partial insights to further comprehend the molecular mechanisms of cuproptosis lncRNAs in sarcoma and could be helpful for the development of personalized therapeutic strategies targeting cuproptosis or cuproptosis lncRNAs.

摘要

铜死亡是一种由铜- elesclomol触发的、依赖线粒体三羧酸(TCA)的新型细胞死亡形式。然而,铜死亡相关lncRNAs在癌症中的潜在机制尚未完全阐明。在此,我们评估了肉瘤中580种与铜死亡相关的lncRNAs,然后利用机器学习方法构建了一个由6种铜死亡lncRNAs组成的模块,命名为CuLncScore。它可以出色地辨别患者的预后,同时区分肿瘤免疫微环境特征。此外,我们通过无监督学习方法模拟铜死亡lncRNAs的分类系统,以促进临床结局和免疫治疗方式选择的区分。值得注意的是,我们的泰州队列验证了CuLncScore和分类系统的稳定性。更进一步,我们通过定量实时聚合酶链反应(qRT-PCR)检测了这6种铜死亡lncRNAs,以确定它们的真实性。总而言之,我们的研究表明,铜死亡lncRNAs参与了肉瘤的各个组成部分,并有助于肿瘤免疫微环境的形成。这些结果为进一步理解铜死亡lncRNAs在肉瘤中的分子机制提供了部分见解,并可能有助于开发针对铜死亡或铜死亡lncRNAs的个性化治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee46/9800909/d4bbaff4cd8c/fcell-10-989882-g001.jpg

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