PMSD11 在肺腺癌中的预后价值和潜在生物功能

IF 2.1 3区 医学 Q3 RESPIRATORY SYSTEM Journal of thoracic disease Pub Date : 2024-11-30 Epub Date: 2024-11-29 DOI:10.21037/jtd-24-1622
Yong Xi, Jing Zeng, Yundong Zhou, Weiyu Shen, Hirokazu Taniguchi, Retnagowri Rajandram, Sivakumar Krishnasamy
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引用次数: 0

摘要

背景:26S非ATP酶调节亚基11(PSMD11)是一种多蛋白复合物,参与泛素化蛋白质的ATP依赖性降解,对胚胎干细胞蛋白酶体活性的调节至关重要。PSMD11 已被证实是导致癌细胞出现和发展的一个因素。然而,PMSD11在肺腺癌(LUAD)中的预后价值和潜在生物功能仍不清楚。本研究旨在全面研究 PSMD11 在 LUAD 中的预后和生物学价值:我们主要致力于全面研究 PSMD11 在 LUAD 患者中的预后和预测价值。此外,我们还旨在通过严格的生物信息学分析,包括表达分析、生存分析、临床病理分析、免疫微环境分析、体细胞突变分析、药物分析和杯突分析,进一步阐明 PSMD11 在 LUAD 肿瘤发生和发展中的潜在机制。随后,我们在非小细胞肺癌(NSCLC)细胞-T细胞共培养模型中研究了PSMD11的表达对免疫逃逸的影响:结果:我们发现 PSMD11 在 LUAD 组织中的表达明显高于正常肺组织。三种临床特征(年龄、分期和总生存事件)在 PSMD11 高表达组和低表达组之间存在显著差异。在生物学功能方面,PSMD11似乎主要在与DNA复制和膜门通道功能相关的通路中发挥致癌作用。值得注意的是,我们观察到 PSMD11 与 T 辅助 2 细胞、γ-δ T 细胞和 T 调节细胞的正相关性最强,而与 B 细胞、肥大细胞和 CD8+ T 细胞的负相关性最高。此外,我们还发现杯突基因(DLAT、DLD 和 PDHA1)的表达与 PSMD11(PConclusions)的表达呈正相关:这些结果表明,PSMD11有可能成为LUAD患者的新型治疗靶点和敏感生物标志物。
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Prognostic value and potential biological function of PMSD11 in lung adenocarcinoma.

Background: The 26S non-ATPase regulatory subunit 11 (PSMD11) is a multiprotein complex that participates in the ATP-dependent degradation of ubiquitinated proteins and is essential to the regulation of embryonic stem cell proteasome activity. PSMD11 has been demonstrated to be a factor contributing to the emergence and progression of cancer cells. However, the prognostic value and potential biological function of PMSD11 in lung adenocarcinoma (LUAD) remains unclear. The aim of this study was to comprehensively investigate the prognostic and biological value of PSMD11 in LUAD.

Methods: We primarily endeavored to comprehensively investigate the prognostic and predictive value of PSMD11 in patients with LUAD. Additionally, we aimed to further clarify the underlying mechanisms of PSMD11 in LUAD tumorigenesis and progression via rigorous bioinformatics analyses, including expression analysis, survival analysis, clinicopathological analysis, immune microenvironment analysis, somatic mutation analysis, drug analysis, and cuproptosis analysis. Subsequently, we examined effect of PSMD11 expression on immune escape in a non-small cell lung cancer (NSCLC) cell-T cell coculture model.

Results: We found that PSMD11 had a significantly higher expression in LUAD tissues than in normal lung tissues. Three clinical characteristics (age, stage, and overall survival event) exhibited significant differences between the PSMD11 high- and low-expression groups. In biological function, PSMD11 appears to exert its tumorigenic effects predominantly in pathways related to DNA replication and membrane-gated channel functions. Notably, we observed that PSMD11 exhibited the strongest positive correlation with T helper 2 cells, gamma-delta T cells, and T regulatory cells and the highest negative correlation with B cells, mast cells, and CD8+ T cells. Furthermore, we found that the expression of cuproptosis genes (DLAT, DLD, and PDHA1) was positively correlated with the expression of PSMD11 (P<0.001).

Conclusions: These results indicate that PSMD11 has the potential to be a novel therapeutic target and sensitive biomarker for patients with LUAD.

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来源期刊
Journal of thoracic disease
Journal of thoracic disease RESPIRATORY SYSTEM-
CiteScore
4.60
自引率
4.00%
发文量
254
期刊介绍: The Journal of Thoracic Disease (JTD, J Thorac Dis, pISSN: 2072-1439; eISSN: 2077-6624) was founded in Dec 2009, and indexed in PubMed in Dec 2011 and Science Citation Index SCI in Feb 2013. It is published quarterly (Dec 2009- Dec 2011), bimonthly (Jan 2012 - Dec 2013), monthly (Jan. 2014-) and openly distributed worldwide. JTD received its impact factor of 2.365 for the year 2016. JTD publishes manuscripts that describe new findings and provide current, practical information on the diagnosis and treatment of conditions related to thoracic disease. All the submission and reviewing are conducted electronically so that rapid review is assured.
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