基于富腺苷酸-尿苷酸(AU)元素基因的肺鳞癌分子亚型鉴定和新预后模型

IF 2.9 4区 医学 Q3 IMMUNOLOGY
Junchao Huang, Siyang Chen, Yakun Liu
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引用次数: 0

摘要

富腺苷酸-尿苷酸元素基因(AREGs)在基因转录后的表达调控中起着至关重要的作用。然而,AREGs在肺鳞癌(LUSC)中的综合作用仍未充分了解。来自TCGA和GTEx数据库的转录组数据,以鉴定差异表达的areg。聚类算法用于识别aregs相关亚型,并通过单变量/多变量和LASSO回归分析建立预后模型。随后,我们创建了一个整合临床病理特征和风险模型的nomogram。使用CIBERSORT、ESTIMATE和MCPcounter分析评估免疫微环境。我们使用RT-qPCR检测了正常和肺鳞癌细胞中特征基因的mRNA表达。最后,我们根据危险患者的特征基因评估对药物的敏感性。两种分子亚型的患者表现出不同的预后和免疫微环境。我们确定了5个具有预后意义的基因,可以作为临床实践中的独立预测因子。低危患者预后较好,而高危患者免疫评分升高,免疫细胞浸润增加,提示免疫治疗反应良好。RT-qPCR结果显示,LUSC中FAM83A和TINAGL1表达上调,FGG和ADH1C表达下调。此外,低危患者对长春瑞滨的敏感性增加。基于areg的分子亚型和预后模型具有可靠的临床预后价值。这一发现可能有助于LUSC患者的个性化和精确治疗,为改善患者预后提供新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of Molecular Subtypes and a Novel Prognostic Model for Lung Squamous Cell Carcinoma Based on Adenylate Uridylate (AU)-Rich Element Genes.

Adenylate uridylate-rich element genes (AREGs) are crucial in modulating gene expression following transcription. However, the comprehensive role of AREGs in lung squamous carcinoma (LUSC) remains inadequately understood. Transcriptome data from TCGA and GTEx databases to identify differentially expressed AREGs. Clustering algorithms were used to identify AREGs-related subtypes, and a prognostic model was developed through univariate/multivariate and LASSO regression analyses. Following this, we created a nomogram integrating clinical pathologic characteristics and the risk model. The immune microenvironment was evaluated using CIBERSORT, ESTIMATE, and MCPcounter analyses. We examined the mRNA expression of the signature genes in normal and lung squamous carcinoma cells using RT-qPCR. Finally, we assessed the sensitivity to drugs based on the signature genes in risk patients. Patients with the 2 identified molecular subtypes exhibit distinct prognoses and immune microenvironments. We identified 5 genes with prognostic significance that can serve as independent predictors in clinical practice. The low-risk patients demonstrates more favorable prognostic outcomes, while the high-risk patients show elevated immune scores and increased immune cell infiltration, suggesting a favorable response to immunotherapy. RT-qPCR results showed upregulation of FAM83A and TINAGL1 and downregulation of FGG and ADH1C in LUSC. In addition, the low-risk patients show increased sensitivity to vinorelbine. The molecular subtypes and prognostic model based on AREGs demonstrate reliable clinical prognostic value. This finding may contribute to personalized and precise treatment for patients with LUSC, offering new insights for improving patient outcomes.

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来源期刊
Journal of Immunotherapy
Journal of Immunotherapy 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
79
审稿时长
6-12 weeks
期刊介绍: Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.
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