scRNA-seq 揭示铜中毒相关蛋白对间皮瘤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.
发表日期:2024 Aug 23
作者:
Jia-Xin Xu, Li-Jing Ma, Li-Ying Tu, Qi-Sheng Tang, Bian Wu, Li-Hong Jiang
来源:
GENES & DEVELOPMENT
摘要:
高侵袭性间皮瘤是腹膜或胸膜的恶性肿瘤。然而,铜凋亡对间皮瘤(MESO)的影响仍不清楚。癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 数据集用于识别与间皮瘤铜凋亡相关的差异基因。然后创建多基因特征来评估疾病的进程。使用单细胞数据和体外验证来揭示关键的基因调控机制。在 MESO 中,我们发现了九个与铜凋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 3 基因特征 (P<0.05),显示出良好的生存时间预测潜力。根据风险评分,低风险亚组患者的生存率显着高于高风险亚组患者(P = 0)。在验证队列中也可以看到类似的生存模式和预测性能。药物敏感性研究结果表明,在高危患者中,长春花碱、紫杉醇、吉非替尼、厄洛替尼为敏感药物(P<0.05)。 CellChat 结果将经典单核细胞确定为与铜凋亡相关的核心细胞。根据细胞亚型分析和体外确认,SLC31A1 参与 M2 巨噬细胞极化的正向调节。与铜凋亡相关的基因对肿瘤免疫有重大影响,并且可以预测 MESO 将如何进展。© 2024。作者。
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.© 2024. The Author(s).