Zhang Jing, Sun Bohao, Lai Jiabin, Kong Weike, Wang Nan, Li Panyuan, Wu Yichen, Jiang Zhaochang
Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
Front Immunol. 2025 May 22;16:1560693. doi: 10.3389/fimmu.2025.1560693. eCollection 2025.
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.
肺腺癌（LUAD）的特征在于肿瘤进展与免疫微环境之间存在复杂的关系。蛋白酶体26S亚基非ATP酶14（PSMD14）在肺腺癌中的功能尚未得到充分阐明，尤其是在其与免疫细胞浸润和患者预后的相关性方面。
本研究的目的是探索PSMD14在肺腺癌中的表达水平，并评估其对肿瘤免疫和临床结果的潜在影响。我们采用了多方面的方法，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，我们还研究了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侵袭性肺腺癌样本中PSMD14的表达。
我们的研究表明，PSMD14在肺腺癌中的表达显著升高，并且与JAMM家族的其他成员，包括真核翻译起始因子3H（EIF3H）和蛋白酶体26S亚基非ATP酶7（PSMD7）呈正相关。重要的是，PSMD14水平升高与患者预后不良相关，表明其作为生物标志物的潜在效用。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的通路显著相关，突出了其在调节细胞增殖和代谢活动中的重要作用。此外，发现PSMD14表达与免疫细胞浸润有关，特别是影响辅助性T细胞和Th2细胞群体，并且与几种免疫检查点分子，如程序性死亡受体1（PD-1）和T细胞免疫球蛋白和ITIM结构域（TIGIT）呈负相关。单细胞RNA测序的结果表明，肺腺癌中表达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。这些发现突出了PSMD14在肺腺癌普遍存在的免疫逃逸策略中的作用。此外，肺腺癌患者的PSMD14蛋白水平显著升高，其表达水平与肿瘤大小、淋巴结受累情况和TNM分期相关。
总之，我们的研究强调了PSMD14在肺腺癌中的关键作用，突出了其作为潜在治疗靶点和预后指标的前景。此外，它为未来的治疗干预开辟了新的途径。
