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鉴定 PSMD11 为一种新型的铜死亡和免疫相关的预后生物标志物,促进肺腺癌的进展。

Identification of PSMD11 as a novel cuproptosis- and immune-related prognostic biomarker promoting lung adenocarcinoma progression.

机构信息

Department of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Tianjin Medical University, Tianjin, China.

Department of Laboratory and Diagnosis, Changhai Hospital, Navy Medical University, Shanghai, China.

出版信息

Cancer Med. 2024 Jun;13(11):e7379. doi: 10.1002/cam4.7379.

Abstract

BACKGROUND

Due to the unfavorable prognosis associated with lung adenocarcinoma (LUAD), the development of targeted therapies and immunotherapies is essential. Cuproptosis, an emerging form of regulated cell death, is implicated in mitochondrial metabolism and is induced by copper ions. This study aimed to explore the prognostic value of cuproptosis- and immune-related genes (CIRGs) in LUAD.

METHODS

We used The Cancer Genome Atlas database to develop a prognostic prediction model for LUAD patients based on eight CIRGs. Using Cox regression analysis, we determined that the CIRG signature is a reliable, independent prognostic factor. We further identified PSMD11 as a critical CIRG and performed immunohistochemistry to study the protein expression levels of PSMD11 in LUAD tissues. We also investigated the impact of PSMD11 on the biological behavior of lung cancer cell lines.

RESULTS

We found that patients with low PSMD11 expression levels displayed an improved prognosis compared with those with high PSMD11 expression levels. Overexpression of PSMD11 enhanced proliferation, migration, invasion, and tumor growth of lung carcinoma cell line A549, while PSMD11 knockdown diminished proliferation, migration, invasion, and tumor growth of lung carcinoma cell line PC9. Additionally, we discovered that PSMD11 expression was positively correlated with the infiltration of myeloid-derived suppressor cells and the increased expression of immunosuppressive molecules.

CONCLUSION

These findings suggest that PSMD11 may serve as a valuable prognostic biomarker and therapeutic target for LUAD.

摘要

背景

由于肺腺癌(LUAD)预后不佳,因此开发靶向治疗和免疫疗法至关重要。铜死亡是一种新兴的受调控的细胞死亡形式,涉及线粒体代谢,由铜离子诱导。本研究旨在探讨与铜死亡和免疫相关基因(CIRGs)在 LUAD 中的预后价值。

方法

我们使用癌症基因组图谱数据库,基于 8 个 CIRGs 为 LUAD 患者开发了一个预后预测模型。通过 Cox 回归分析,我们确定 CIRG 特征是一个可靠的、独立的预后因素。我们进一步确定 PSMD11 为关键的 CIRG,并通过免疫组织化学研究 PSMD11 在 LUAD 组织中的蛋白表达水平。我们还研究了 PSMD11 对肺癌细胞系生物学行为的影响。

结果

我们发现,与 PSMD11 高表达的患者相比,PSMD11 低表达的患者预后更好。PSMD11 的过表达增强了肺癌细胞系 A549 的增殖、迁移、侵袭和肿瘤生长,而 PSMD11 的敲低则减弱了肺癌细胞系 PC9 的增殖、迁移、侵袭和肿瘤生长。此外,我们发现 PSMD11 的表达与髓源性抑制细胞的浸润和免疫抑制分子的表达增加呈正相关。

结论

这些发现表明,PSMD11 可能是 LUAD 的一个有价值的预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c40/11165170/1e27dfcca1a4/CAM4-13-e7379-g005.jpg

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