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单细胞RNA测序揭示铜死亡相关蛋白对间皮瘤中巨噬细胞极化的影响

The Effect of Cuproptosis-Related Proteins on Macrophage Polarization in Mesothelioma is Revealed by scRNA-seq.

作者信息

Xu Jia-Xin, Ma Li-Jing, Tu Li-Ying, Tang Qi-Sheng, Wu Bian, Jiang Li-Hong

机构信息

Faculty of Life Science and Technology, Kunming University of Science and Technology, Chenggong District, Kunming, 400042, China.

Department of General Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.

出版信息

Biol Trace Elem Res. 2025 Apr;203(4):1898-1908. doi: 10.1007/s12011-024-04333-y. Epub 2024 Aug 23.

Abstract

High invasiveness mesothelioma is a malignant tumor of the peritoneum or pleura. The effect of cuproptosis on mesothelioma (MESO) is still unknown, though. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets were used to identify differential genes linked to cuproptosis in mesothelioma. Multigene features were then created to assess the course of the disease. Use single-cell data and in vitro validation to uncover crucial gene regulation mechanisms. In MESO, we found nine differentially expressed genes linked to cuproptosis. Using univariate Cox and LASSO regression techniques, a 3-gene feature (P < 0.05) was created, showing a good predictive potential for survival time. According to the risk score, patients in the low-risk subset had a considerably greater survival rate than those in the high-risk subset (P = 0). The similar survival pattern and prediction performance are also seen in the validation queue. The findings of the drug sensitivity research indicate that in high-risk patients, vinblastine, paclitaxel, gefitinib, and erlotinib are sensitive medications (P < 0.05). Classical monocytes were identified as core cells connected to cuproptosis by the CellChat results. SLC31A1 is implicated in the positive regulation of M2 macrophage polarization, according to cell subtype analysis and in vitro confirmation. Genes linked to cuproptosis have a major influence on tumor immunity and can predict how MESO will progress.

摘要

高侵袭性间皮瘤是一种腹膜或胸膜的恶性肿瘤。不过,铜死亡对间皮瘤(MESO)的影响尚不清楚。利用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)数据集来识别间皮瘤中与铜死亡相关的差异基因。然后创建多基因特征以评估疾病进程。利用单细胞数据和体外验证来揭示关键的基因调控机制。在间皮瘤中,我们发现了9个与铜死亡相关的差异表达基因。使用单变量Cox和LASSO回归技术,创建了一个三基因特征(P < 0.05),对生存时间显示出良好的预测潜力。根据风险评分,低风险亚组患者的生存率明显高于高风险亚组患者(P = 0)。在验证队列中也观察到了类似的生存模式和预测性能。药物敏感性研究结果表明,在高风险患者中,长春碱、紫杉醇、吉非替尼和厄洛替尼是敏感药物(P < 0.05)。CellChat结果将经典单核细胞鉴定为与铜死亡相关的核心细胞。根据细胞亚型分析和体外验证,SLC31A1参与M2巨噬细胞极化的正调控。与铜死亡相关的基因对肿瘤免疫有重大影响,并可预测间皮瘤的进展情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6da0/11920352/b351291f1c29/12011_2024_4333_Fig1_HTML.jpg

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