SARS-CoV-2感染通过谷氨酰胺调节对肺腺癌患者免疫细胞铜凋亡的影响。
Impact of SARS-CoV-2 infection on immune cell cuproptosis in patients with lung adenocarcinoma via glutamine regulation.
发表日期:2024 Aug 10
作者:
Dan Wang, Xijin Deng, Shanshan Li, Si Ri Gu Leng Sana
来源:
INTERNATIONAL IMMUNOPHARMACOLOGY
摘要:
肺腺癌 (LA) 是最常见的肺癌类型,死亡率很高,尤其是在既往感染过冠状病毒病 (COVID-19) 的癌症患者中。因此,本研究旨在探讨临床环境中 COVID-19 加剧 LA 进展的机制。实验涉及从三组收集血清样本:健康对照组 (Con,n = 20)、肺腺癌组 (LA ,n = 30),以及一组首次感染 COVID-19 的肺腺癌患者(C-LA,n = 58)。采用液相色谱-质谱法对代谢物进行分析,并通过生物信息学分析鉴定差异表达的代谢物。测定Con组和C-LA组患者血清中谷胱甘肽(GSH)、活性氧(ROS)和铜离子(Cu2+)的浓度。使用电子显微镜观察单核细胞和淋巴细胞的线粒体形态变化。代谢组学分析显示142种不同的代谢物,其中谷氨酰胺(Gln)表达在C-LA组中显着降低。与Con组相比,C-LA组GSH显着降低,ROS和Cu2+显着增加。进一步的研究发现,C-LA组的单核细胞和淋巴细胞的线粒体表现出相应的改变,表明铜凋亡。SARS-CoV-2感染可能会降低Gln水平,导致GSH水平降低、铜超载和免疫细胞死亡增加。这可能会进一步加剧肿瘤的快速发展。因此,谷氨酰胺调节在 COVID-19 患者的 LA 进展中发挥着重要作用,并代表了潜在的治疗靶点。版权所有 © 2024。由 Elsevier B.V. 出版。
Lung adenocarcinoma (LA), the most prevalent type of lung cancer, is associated with a high mortality rate, especially among patients with cancer previously infected with coronavirus disease (COVID-19). Therefore, this study aimed to explore the mechanisms by which COVID-19 exacerbates LA progression in a clinical setting.The experiment involved collecting serum samples from three groups: a healthy control group (Con, n = 20), a lung adenocarcinoma group (LA, n = 30), and a group of lung adenocarcinoma patients with first-time COVID-19 infection (C-LA, n = 58). Metabolites were analyzed using liquid chromatography-mass spectrometry, and differentially expressed metabolites were identified through bioinformatics analysis. The concentrations of glutathione (GSH), reactive oxygen species (ROS), and copper ions (Cu2+) in the serum of patients in the Con and C-LA groups were measured. Mitochondrial morphological changes in monocytes and lymphocytes were observed using electron microscopy.Metabolomic analysis revealed 142 distinct metabolites, among which glutamine (Gln) expression was significantly decreased in the C-LA group. Compared to the Con group, the C-LA group showed a significant decrease in GSH and a notable increase in ROS and Cu2+. Further research revealed that the mitochondria of monocytes and lymphocytes in the C-LA group exhibited corresponding alterations indicative of cuproptosis.SARS-CoV-2 infection may reduce Gln levels, leading to reduced GSH levels, copper overload, and increased death of immune cells, which may further exacerbate rapid tumor development. Thus, glutamine regulation plays an important role in LA progression in patients with COVID-19 and represents a potential therapeutic target.Copyright © 2024. Published by Elsevier B.V.