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四种RNA修饰书写相关长链非编码RNA特征在肺腺癌中的预后价值及免疫景观

Prognostic Value and Immune Landscapes of Four Types of RNA Modification Writer-Related LncRNAs Signature in Lung Adenocarcinoma.

作者信息

Qian Yongmei, Zhang Qicheng, Ren Yinghui, Cao Limin, Zheng Sijia, Li Bingbing, Wu Xiang, Meng Zhaowei, Xu Ke

机构信息

Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.

Department of Anesthesiology, Tianjin First Central Hospital, Tianjin 300192, China.

出版信息

J Cancer. 2024 Jul 9;15(15):4818-4837. doi: 10.7150/jca.96755. eCollection 2024.

Abstract

Lung adenocarcinoma (LUAD) is the predominant pathological subtype of non-small cell lung cancer (NSCLC). The four primary forms of RNA adenosine modifications, N6-methyladenosine (mA), N1-methyladenosine (mA), alternative polyadenylation (APA) and adenosine-to-inosine (A-to-I) RNA editing, play a critical role in tumor progression. However, the clinical significance of RNA modification writer-related long non-coding RNAs (lncRNAs) in LUAD remains unclear. The Cancer Genome Atlas (TCGA) database was used to obtain transcriptomic and clinicopathological data. Univariate Cox regression analysis, consensus cluster analysis, and least absolute shrinkage and selection operator (LASSO) Cox regression were used to establish the molecular subtypes and prognostic signatures of LUAD based on the expression levels of lncRNAs. ESTIMATE, CIBERSORT, ssGSEA, and TIDE algorithms were used to investigate immune cell infiltration and immunotherapy. In addition, IC of chemotherapeutic agents were calculated for different risk subgroups using the "pRRophetic" R package. Finally, the expression of prognosis-associated lncRNAs in lung cancer tissues was verified using qPCR. A prognostic risk signature containing seven lncRNAs associated with four types of RNA modification writers was established. The high-risk group had a poorer prognosis and higher clinicopathological grade. Most immune checkpoint genes and immune cell infiltration differed significantly between the two risk groups. The high-risk group had a higher tumor mutation burden (TMB), lower TIDE score, and was more sensitive to immunotherapy. We developed an RNA modification writer-related seven-lncRNA signature prognostic model that was associated with prognosis, tumor microenvironment, and response to immunotherapy in LUAD patients. Among them, LINC01352, AC024075.1, AC005070.3, AL133445.2, AC005856.1, and LINC00968 were downregulated in LUAD, whereas AC092168.2 was upregulated. This model may be a valuable tool for personalized LUAD therapies.

摘要

肺腺癌(LUAD)是非小细胞肺癌(NSCLC)的主要病理亚型。RNA腺苷修饰的四种主要形式,即N6-甲基腺苷(m6A)、N1-甲基腺苷(m1A)、可变聚腺苷酸化(APA)和腺苷到肌苷(A-to-I)RNA编辑,在肿瘤进展中起关键作用。然而,RNA修饰书写相关长链非编码RNA(lncRNA)在LUAD中的临床意义仍不清楚。利用癌症基因组图谱(TCGA)数据库获取转录组和临床病理数据。采用单因素Cox回归分析、共识聚类分析和最小绝对收缩和选择算子(LASSO)Cox回归,基于lncRNA的表达水平建立LUAD的分子亚型和预后特征。运用ESTIMATE、CIBERSORT、ssGSEA和TIDE算法研究免疫细胞浸润和免疫治疗。此外,使用“pRRophetic”R包计算不同风险亚组化疗药物的抑制浓度(IC)。最后,采用qPCR验证肺癌组织中预后相关lncRNA的表达。建立了一个包含与四种RNA修饰书写相关的7个lncRNA的预后风险特征。高危组预后较差,临床病理分级较高。两个风险组之间大多数免疫检查点基因和免疫细胞浸润存在显著差异。高危组肿瘤突变负荷(TMB)较高,TIDE评分较低,对免疫治疗更敏感。我们开发了一种与RNA修饰书写相关的7-lncRNA特征预后模型,该模型与LUAD患者的预后、肿瘤微环境和免疫治疗反应相关。其中,LINC01352、AC024075.1、AC005070.3、AL133445.2、AC005856.1和LINC00968在LUAD中表达下调,而AC092168.2表达上调。该模型可能是LUAD个性化治疗的有价值工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7973/11310873/1caab33f9ee1/jcav15p4818g001.jpg

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