建立和验证肺腺癌 PSMB6 的免疫调节和预后预测模型

IF 2.8 3区 生物学 Q2 GENETICS & HEREDITY
Frontiers in Genetics Pub Date : 2024-10-23 eCollection Date: 2024-01-01 DOI:10.3389/fgene.2024.1458047
Haiyang Zhao, Kexin Luo, Meihan Liu, Yuanze Cai, Siman Liu, Shijuan Li, Yongsheng Zhao, Hongpan Zhang
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引用次数: 0

摘要

肺癌是最常见的恶性肿瘤之一,患者往往在确诊时已是晚期,对人类健康构成重大威胁,因此建立一个预测肺癌患者预后的模型至关重要。最近的研究表明,蛋白酶体 20S 亚基 6(PSMB6)可能与不同肿瘤细胞的抗凋亡通路和增殖转导信号密切相关。然而,PSMB6在肺腺癌(LUAD)免疫调节过程中的确切作用仍有待阐明。通过分析TCGA数据库,我们发现PSMB6的表达与肿瘤生长趋势呈正相关,PSMB6表达水平升高的肺腺癌患者预后较差。我们的研究结果表明,PSMB6表达水平、免疫细胞浸润和免疫检查点基因表达之间存在密切的相关性,这表明PSMB6可能成为一个新的独立预后指标。此外,我们还通过分析PSMB6与免疫微环境之间的联系,建立了PSMB6调控的免疫浸润相关基因的预后模型。该模型不仅能预测肺腺癌的预后,还能预测患者对免疫疗法的反应。这一研究成果的有效性已得到 GSE31210 和 IMvigor210 队列的证实。对 Kaplan-Meier Plotter 数据库的分析表明,PSMB6 表达水平升高的个体预后较差。此外,体外实验表明,敲除 PSMB6 可抑制肺腺癌细胞的增殖、迁移和侵袭,同时促进其凋亡。总之,我们的研究结果表明,PSMB6 可显著影响肺腺癌的管理和治疗,为靶向免疫治疗策略开辟了新途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Immune regulation and prognostic prediction model establishment and validation of PSMB6 in lung adenocarcinoma.

Lung cancer is one of the most common malignant tumors, and patients are often diagnosed at an advanced stage, posing a substantial risk to human health, so it is crucial to establish a model to forecast the prognosis of patients with lung cancer. Recent research has indicated that proteasome 20S subunit 6 (PSMB6) may be closely associated with anti-apoptotic pathways, and proliferation transduction signals in tumor cells of different tumors. However, the precise role of PSMB6 in the immunoregulatory processes within lung adenocarcinoma (LUAD) is yet to be elucidated. By analyzing the TCGA database, we discovered a positive correlation between the expression of PSMB6 and tumor growth trends, and lung adenocarcinoma patients with elevated PSMB6 expression levels had a worse prognosis. Our findings suggest a close correlation between PSMB6 expression levels, immune cell infiltration and immune checkpoint gene expression, which suggests that PSMB6 may become a new independent prognostic indicator. In addition, we developed a prognostic model of PSMB6-regulated immune infiltration-associated genes by analyzing the link between PSMB6 and the immune microenvironment. This model can not only predict the prognosis of lung adenocarcinoma but also forecasts the patient's reaction to immunotherapy. The validity of this research outcome has been confirmed by the GSE31210 and IMvigor210 cohorts. Analysis of the Kaplan-Meier Plotter database indicates that individuals with elevated levels of PSMB6 expression exhibit a poorer prognosis. Additionally, in vitro experiments demonstrated that knockdown of PSMB6 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells while promoting their apoptosis. Overall, our findings suggest that PSMB6 could remarkably influence the management and treatment of lung adenocarcinoma, opening new avenues for targeted immunotherapeutic strategies.

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来源期刊
Frontiers in Genetics
Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
5.50
自引率
8.10%
发文量
3491
审稿时长
14 weeks
期刊介绍: Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.
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