RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The impact of neddylation on prognosis in the immune microenvironment of neuroblastoma: a single-cell transcriptomic analysis.
The impact of neddylation on prognosis in the immune microenvironment of neuroblastoma: a single-cell transcriptomic analysis.
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神经母细胞瘤(NB)是儿童中常见的恶性肿瘤,主要影响神经系统,死亡率高,尤其是高危患者。本研究旨在通过分析NB患者的基因表达数据,建立neddylation相关预后特征(NRPS),并评估其临床应用潜力。
我们采用基因表达谱分析、单细胞RNA测序(scRNA-seq)、加权基因共表达网络分析(WGCNA)和单样本基因集富集分析(ssGSEA)进行综合分析,以阐明neddylation的作用并为NB患者建立NRPS。
我们的分析识别了171,992个细胞,分为19个不同的簇,揭示施万细胞和肿瘤细胞的neddylation评分显著高于其他细胞类型。
我们构建了一个对总生存期和无事件生存期有显著影响的NRPS。免疫浸润分析显示,低风险组中免疫细胞水平显著更高,尤其是活化的CD8+ T细胞和NK 细胞,表明抗肿瘤免疫反应更强。
此外,基因集富集分析(GSEA)显示,高风险组与细胞分裂和DNA修复通路相关,而低风险组则富集于免疫相关信号通路,提示免疫激活可能具有保护作用。
此外,免疫治疗分析表明,低风险评分组表现出更好的免疫治疗结果。本研究强调了NRPS在预测NB患者生存和治疗结局中的临床意义,突出了其在个性化治疗方法中的必要性和紧迫性。
Neuroblastoma (NB) is a prevalent malignant tumor in children, primarily affecting the nervous system, with a high mortality rate, particularly in high-risk patients.
This study aims to establish a neddylation-related prognostic signature (NRPS) through the analysis of gene expression data from NB patients and to evaluate its clinical application potential. A comprehensive analysis was conducted using gene expression profiling, single-cell RNA sequencing (scRNA-seq), weighted gene co-expression network analysis (WGCNA), and single-sample gene set enrichment analysis (ssGSEA) to elucidate the role of neddylation and establish a NRPS for NB patients.
Our analysis identified 171,992 cells categorized into 19 distinct clusters, revealing that Schwann and tumor cells exhibited significantly higher neddylation scores compared to other cell types.
We constructed a NRPS that significantly impacts overall survival and event-free survival. Immune infiltration analysis demonstrated significantly higher levels of immune cells, particularly activated CD8 + T cells and natural killer cells, in the low-risk group, indicating a stronger anti-tumor immune response.
Furthermore, gene set enrichment analysis (GSEA) revealed that the high-risk group was associated with cell division and DNA repair pathways, while the low-risk group showed enrichment in immune-related signaling pathways, suggesting immune activation may confer protective effects.
Additionally, the immunotherapy analysis suggested that the low-risk score group exhibited better immunotherapy outcomes.
This study underscores the clinical significance of NRPS in predicting survival and therapeutic outcomes in NB patients, highlighting their necessity and urgency in personalized treatment approaches.
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