Xi Yong, Zeng Jing, Zhou Yundong, Shen Weiyu, Taniguchi Hirokazu, Rajandram Retnagowri, Krishnasamy Sivakumar
Division of Cardiothoracic Surgery, Department of Surgery, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
Department of Surgery, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
J Thorac Dis. 2024 Nov 30;16(11):7819-7835. doi: 10.21037/jtd-24-1622. Epub 2024 Nov 29.
The 26S non-ATPase regulatory subunit 11 () 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. 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 in lung adenocarcinoma (LUAD) remains unclear. The aim of this study was to comprehensively investigate the prognostic and biological value of in LUAD.
We primarily endeavored to comprehensively investigate the prognostic and predictive value of in patients with LUAD. Additionally, we aimed to further clarify the underlying mechanisms of 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 expression on immune escape in a non-small cell lung cancer (NSCLC) cell-T cell coculture model.
We found that 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 high- and low-expression groups. In biological function, appears to exert its tumorigenic effects predominantly in pathways related to DNA replication and membrane-gated channel functions. Notably, we observed that 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 (, and ) was positively correlated with the expression of (P<0.001).
These results indicate that has the potential to be a novel therapeutic target and sensitive biomarker for patients with LUAD.
26S非ATP酶调节亚基11（）是一种多蛋白复合体，参与泛素化蛋白的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。已被证明是癌细胞出现和进展的一个因素。然而，在肺腺癌（LUAD）中的预后价值和潜在生物学功能仍不清楚。本研究的目的是全面调查在LUAD中的预后和生物学价值。
我们主要致力于全面调查在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表达对免疫逃逸的影响。
我们发现，在LUAD组织中的表达明显高于正常肺组织。高表达组和低表达组在三个临床特征（年龄、分期和总生存事件）上存在显著差异。在生物学功能方面，似乎主要在与DNA复制和膜门控通道功能相关的途径中发挥其致瘤作用。值得注意的是，我们观察到与辅助性T细胞2、γδT细胞和调节性T细胞表现出最强的正相关，与B细胞、肥大细胞和CD8 T细胞表现出最高的负相关。此外，我们发现铜死亡基因（、和）的表达与的表达呈正相关（P<0.001）。
这些结果表明，有可能成为LUAD患者的新型治疗靶点和敏感生物标志物。
