一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CMSS1: A RNA binding protein with pivotal roles in non-small cell lung cancer progression and prognosis.
CMSS1: A RNA binding protein with pivotal roles in non-small cell lung cancer progression and prognosis.
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我们的研究结果表明,CMSS1 可能作为 NSCLC 患者的预后指标和治疗靶点。本研究可能为 NSCLC 患者的精准治疗和准确预后预测提供潜在指导。
Cms1核糖体小亚基同源物(CMSS1)是一种RNA结合蛋白(RBP),在肿瘤发展中起关键作用。然而,CMSS1在非小细胞肺癌(NSCLC)中的预后和免疫学作用仍不清楚。
利用癌症基因组图谱(TCGA)数据库鉴定差异表达的RBP基因,并通过单因素Cox回归分析和Kaplan-Meier检验筛选出核心RBP相关基因CMSS1。为评估CMSS1的预后能力,进行了时间依赖性受试者工作特征曲线、Kaplan-Meier曲线和多因素Cox回归分析。使用ImmuCellAI算法评估CMSS1基因与肿瘤浸润免疫细胞之间的关系。此外,进行了功能缺失实验以探究CMSS1在NSCLC细胞中的功能作用。
生物信息学分析显示,CMSS1,一个RBP相关基因,在NSCLC肿瘤中显著上调,其RNA水平升高与NSCLC患者的不良预后相关。免疫细胞浸润分析显示,CMSS1表达与CD4 T细胞呈负相关,与巨噬细胞和Tregs呈正相关。此外,RT-qPCR和western blot证实了NSCLC细胞系中CMSS1 mRNA和CMSS1蛋白水平升高。值得注意的是,CMSS1的下调抑制了NSCLC细胞的活力、迁移和侵袭。
The Cms1 ribosomal small subunit homolog (CMSS1), an RNA-binding protein (RBP), plays a crucial role in tumor development. However, the prognostic and immunological role of CMSS1 in non-small cell lung cancer (NSCLC) remains unclear.
Differentially expressed RBP genes were identified using The Cancer Genome Atlas (TCGA) database, and the hub RBP-related gene, CMSS1, was selected through univariate Cox regression analysis and Kaplan-Meier tests. To evaluate the prognostic capacity of the CMSS1, time-dependent receiver operating characteristic curves, Kaplan-Meier curves and multivariate Cox regression analyses were conducted. The relationship between the CMSS1 gene and tumor-infiltrating immune cells was assessed using the ImmuCellAI algorithm. Additionally, a loss-of-function assay was performed to investigate the functional role of CMSS1 in NSCLC cells.
Bioinformatic analysis revealed that CMSS1, an RBP-related gene, was notably upregulated in NSCLC tumors, with elevated RNA levels correlating with poor prognosis in NSCLC patients. Immune cell infiltration analysis showed that CMSS1 expression was negatively correlated with CD4 T cells and was positively correlated with macrophages and Tregs. Furthermore, RT-qPCR and western blot confirmed the increased CMSS1 mRNA and CMSS1 protein levels in NSCLC cell lines. Significantly, downregulation of CMSS1 inhibited NSCLC cell viability, migration and invasion.
Our findings suggest that CMSS1 may serve as both a prognostic indicator and a therapeutic target for patients with NSCLC. This study may provide potential guidance for precision therapy and accurate prognosis prediction for patients with NSCLC.
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