一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
PMSD11 在肺腺癌中的预后价值及潜在生物学功能
英文原题：Prognostic value and potential biological function of PMSD11 in lung adenocarcinoma.
查看英文原题
Prognostic value and potential biological function of PMSD11 in lung adenocarcinoma.
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研究概要
这些结果表明，PSMD11 有潜力成为 LUAD 患者的新型治疗靶点和敏感生物标志物。
研究思路结论见上方概要
背景
26S非ATP酶调节亚基11（PSMD11）是一种多蛋白复合物，参与泛素化蛋白的ATP依赖性降解，并且对胚胎干细胞蛋白酶体活性的调控至关重要。PSMD11已被证实是促进癌细胞发生和发展的一个因素。然而，PMSD11在肺腺癌（LUAD）中的预后价值及潜在生物学功能仍不清楚。本研究旨在全面探讨PSMD11在LUAD中的预后和生物学价值。
方法
我们主要致力于全面探究PSMD11在LUAD患者中的预后和预测价值。此外，我们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、药物分析和铜死亡分析，进一步阐明PSMD11在LUAD肿瘤发生和进展中的潜在机制。随后，我们在非小细胞肺癌（NSCLC）细胞-T细胞共培养模型中检测了PSMD11表达对免疫逃逸的影响。
结果
我们发现PSMD11在LUAD组织中的表达显著高于正常肺组织。三个临床特征（年龄、分期和总生存期事件）在PSMD11高表达组和低表达组之间表现出显著差异。在生物学功能方面，PSMD11似乎主要在DNA复制和膜门控通道功能相关通路中发挥其致瘤作用。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调节细胞呈最强的正相关，与B细胞、肥大细胞和CD8+ T细胞呈最高的负相关。此外，我们发现铜死亡基因（DLAT、DLD和PDHA1）的表达与PSMD11的表达呈正相关（P<0.001）。
展开英文摘要原文
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.
论文信息
- 作者
- Xi Y、Zeng J、Zhou Y、Shen W、Taniguchi H、Rajandram R、Krishnasamy S
- 单位
- Division of Cardiothoracic Surgery, Department of Surgery, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.Malaysia
- 期刊
- Journal of thoracic disease2024 Nov 30
- 原文标识
- PubMed 39678883 · DOI 10.21037/jtd-24-1622
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