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肺腺癌中 PSMD14 的表达及其对免疫细胞浸润和预后的影响:基于 RNA 和单细胞 RNA 测序的综合分析

英文原题:Expression of PSMD14 in lung adenocarcinoma and its impact on immune cell infiltration and prognosis: a comprehensive analysis based on RNA and single-cell RNA sequencing.

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Expression of PSMD14 in lung adenocarcinoma and its impact on immune cell infiltration and prognosis: a comprehensive analysis based on RNA and single-cell RNA sequencing.

PubMed 2025/05/22(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

我们的研究强调了 PSMD14 在 LUAD 中的关键作用,突显了其作为潜在治疗靶点和预后指标的潜力。此外,它为未来的治疗干预开辟了新的途径。

研究思路结论见上方概要

肺腺癌(LUAD)的显著特征是肿瘤进展与免疫微环境之间错综复杂的关系。PSMD14(蛋白酶体26S亚基,非ATP酶14)在LUAD中的作用尚未充分阐明,尤其是其与免疫细胞浸润及患者预后之间的相关性。

本研究旨在探讨PSMD14在LUAD中的表达水平,并评估其对肿瘤免疫和临床结局的潜在影响。采用多方面的方法,包括分析RNA测序(RNA-seq)数据、评估免疫细胞浸润、生存分析、基因富集分析以及整合单细胞RNA-seq数据,以全面评估PSMD14的生物学相关性。此外,我们还检查了PSMD14表达与临床参数之间的相关性。采用免疫组织化学技术分析浸润性肺腺癌样本中PSMD14的表达。

我们的研究表明,PSMD14在LUAD中表达显著升高,并与其他JAMM家族成员(包括EIF3H和PSMD7)呈正相关。重要的是,PSMD14水平升高与患者不良预后相关,提示其作为生物标志物的潜在价值。此外,京都基因与基因组百科全书(KEGG)通路分析显示,PSMD14与细胞周期和尼古丁依赖相关通路显著相关,突显了其在调控细胞增殖和代谢活动中的重要功能。进一步发现,PSMD14表达与免疫细胞浸润相关,尤其影响T辅助细胞和Th2细胞群体,并与PD-1和TIGIT等多种免疫检查点分子呈负相关。单细胞RNA测序结果鉴定出LUAD中表达PSMD14的免疫细胞类型包括树突状细胞(DC)、单核细胞和组织干细胞。这些发现凸显了PSMD14在LUAD中普遍存在的免疫逃逸策略中的作用。此外,LUAD患者中PSMD14蛋白水平显著升高,其表达水平与肿瘤大小、淋巴结受累及TNM分类相关。

展开英文摘要原文

Lung adenocarcinoma (LUAD) is distinguished by intricate relationships between tumor advancement and the immune microenvironment. The function of PSMD14 (Proteasome 26S Subunit, Non-ATPase 14) within the context of LUAD is not well elucidated, especially in terms of its correlation with immune cell infiltration and the prognosis of patients.

The objective of this research was to explore the expression levels of PSMD14 in LUAD and to evaluate its potential implications for tumor immunity and clinical outcomes. A multifaceted approach was adopted, which included the analysis of RNA sequencing (RNA-seq) data, assessment of immune cell infiltration, survival analysis, gene enrichment analysis, and integration of single-cell RNA-seq data to thoroughly evaluate the biological relevance of PSMD14. Furthermore, we examined the correlation between PSMD14 expression and clinical parameters. Immunohistochemistry techniques were employed to analyze PSMD14 expression in samples of invasive pulmonary adenocarcinoma.

Our study demonstrated that the expression of PSMD14 is markedly elevated in LUAD and exhibits a positive correlation with other members of the JAMM family, including EIF3H and PSMD7. Importantly, elevated levels of PSMD14 were linked to poor patient prognosis, indicating its potential utility as a biomarker. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that PSMD14 is significantly associated with pathways related to the cell cycle and nicotine dependence, underscoring its vital function in modulating cell proliferation and metabolic activities. Furthermore, PSMD14 expression was found to be associated with the infiltration of immune cells, particularly influencing T helper and Th2 cell populations, and exhibited an inverse relationship with several immune checkpoint molecules, such as PD-1 and TIGIT. Insights from single-cell RNA sequencing identified that PSMD14-expressing immune cell types in LUAD include dendritic cell (DC), monocytes, and tissue stem cells. These findings highlight the role of PSMD14 in the immune evasion strategies prevalent in LUAD. Additionally, a notable increase in PSMD14 protein levels was recorded in LUAD patients, with expression levels correlating with tumor size, lymph node involvement, and the TNM classification.

In summary, our research underscores the crucial role of PSMD14 in LUAD, highlighting its promise as a potential target for therapy and a prognostic indicator. Furthermore, it opens up novel approaches for future therapeutic interventions.

论文信息

作者
Zhang J、Sun B、Lai J、Kong W、Wang N、Li P、Wu Y、Jiang Z
单位
Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.China
期刊
Frontiers in immunology2025
原文标识
PubMed 40475775 · DOI 10.3389/fimmu.2025.1560693