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综合批量和单细胞RNA测序揭示了神经母细胞瘤中一种与铜死亡相关的长链非编码RNA预后特征。

Integrated bulk and single-cell RNA sequencing reveals a cuproptosis-related LncRNA prognostic signature in neuroblastoma.

作者信息

Chen Ke, Wang Jing, Yang Shimin, Xiao Jun, Wu Luyao, Li Zejian, Zhao Xiang, Chen Xuyong, Li Honglin, Feng Jiexiong, Meng Xinyao

机构信息

Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.

Hubei Clinical Center of Hirschsprung's Disease and Allied Dsorders, Wuhan, 430030, China.

出版信息

BMC Cancer. 2025 Jul 1;25(1):1076. doi: 10.1186/s12885-025-14463-8.


DOI:10.1186/s12885-025-14463-8
PMID:40596995
Abstract

BACKGROUND: Neuroblastoma (NB), the most common extracranial solid tumor of childhood, originates from developing sympathetic nervous system. While cuproptosis has emerged as a critical regulator in oncobiology, its mechanistic involvement in NB remains poorly characterized. METHODS: RNA-seq data of NB patients was analyzed using limma and ClusterProfiler. CRlncRNAs were identified through Pearson correlation between lncRNAs and CRGs, with co-expression networks visualized via ggalluvial. Prognostic signature was constructed through Lasso-penetrated Cox regression and validated via EFS analysis, C-index, and ROC curves. Somatic mutations and TMB were profiled using maftools. Immune infiltration landscapes were deciphered by CIBERSORT, while single-cell analysis integrated AddModuleScore, AUCell, and inferCNV to map CNV-driven transcriptional heterogeneity. Functional validation via siRNA knockdown confirmed the oncogenic role of CRGs. RESULTS: The risk model: Risk Score = (-1.637×DIRC3-AS1) + (0.6758×FOXN3-AS1) + (0.3032×LINC00682) + (-0.6812×RASSF8-AS1) was constructed. Stratification by median risk score revealed significantly prolonged EFS and OS. No significant TMB difference was observed between subgroups. scRNA-seq analysis highlighted malignant cell dominance with marked CNVs in high-risk patients. Functional validation confirmed CRlncRNAs' roles in modulating proliferation and migration. CONCLUSION: Our findings establish a novel prognostic framework for NB that enhances risk stratification accuracy and provides actionable biomarkers to guide precision clinical management.

摘要

背景:神经母细胞瘤(NB)是儿童最常见的颅外实体瘤,起源于发育中的交感神经系统。虽然铜死亡已成为肿瘤生物学中的关键调节因子,但其在NB中的机制仍知之甚少。 方法:使用limma和ClusterProfiler分析NB患者的RNA-seq数据。通过lncRNA与CRG之间的Pearson相关性鉴定CRlncRNAs,并通过ggalluvial可视化共表达网络。通过Lasso-penetrated Cox回归构建预后特征,并通过无事件生存期(EFS)分析、C指数和ROC曲线进行验证。使用maftools分析体细胞突变和肿瘤突变负荷(TMB)。通过CIBERSORT解读免疫浸润景观,而单细胞分析整合AddModuleScore、AUCell和inferCNV来绘制CNV驱动的转录异质性图谱。通过siRNA敲低进行功能验证,证实了CRG的致癌作用。 结果:构建了风险模型:风险评分=(-1.637×DIRC3-AS1)+(0.6758×FOXN3-AS1)+(0.3032×LINC00682)+(-0.6812×RASSF8-AS1)。根据中位风险评分分层显示EFS和总生存期(OS)显著延长。亚组之间未观察到显著的TMB差异。单细胞RNA测序(scRNA-seq)分析突出了高危患者中恶性细胞的优势以及明显的CNV。功能验证证实了CRlncRNAs在调节增殖和迁移中的作用。 结论:我们的研究结果为NB建立了一个新的预后框架,提高了风险分层的准确性,并提供了可指导精准临床管理的可操作生物标志物。

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Integrated bulk and single-cell RNA sequencing reveals a cuproptosis-related LncRNA prognostic signature in neuroblastoma.

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本文引用的文献

[1]
RASSF8-AS1 displays low expression in colorectal cancer and up-regulates RASSF8 to suppress cell invasion and migration.

Pathol Res Pract. 2022-9

[2]
Comprehensive Analysis of Cuproptosis-Related Genes in Immune Infiltration and Prognosis in Melanoma.

Front Pharmacol. 2022-6-28

[3]
A novel Cuproptosis-related LncRNA signature to predict prognosis in hepatocellular carcinoma.

Sci Rep. 2022-7-5

[4]
A Novel Cuproptosis-Related Prognostic Gene Signature and Validation of Differential Expression in Clear Cell Renal Cell Carcinoma.

Genes (Basel). 2022-5-10

[5]
Copper induces cell death by targeting lipoylated TCA cycle proteins.

Science. 2022-3-18

[6]
Copper-induced cell death.

Science. 2022-3-18

[7]
Identification and Validation of Ferroptosis-Related LncRNA Signatures as a Novel Prognostic Model for Colon Cancer.

Front Immunol. 2021

[8]
Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis.

Nat Commun. 2021-12-15

[9]
Identification of Immune-Related lncRNA Prognostic Signature and Molecular Subtypes for Glioblastoma.

Front Immunol. 2021

[10]
Connecting copper and cancer: from transition metal signalling to metalloplasia.

Nat Rev Cancer. 2022-2

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