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用于前庭神经鞘瘤肿瘤生长机制的23基因特征的开发。

Development of a 23-Gene Signature for Tumor Growth Mechanism in Vestibular Schwannoma.

作者信息

Sung Ji-Yong, Lee Jung Woo

机构信息

Department of Research & Development, VeraOmics, 138 Seoksanro, Namdong-gu, Incheon 21551, Republic of Korea.

Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea.

出版信息

Cancers (Basel). 2024 Dec 11;16(24):4134. doi: 10.3390/cancers16244134.

DOI:10.3390/cancers16244134
PMID:39766034
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11674088/
Abstract

: Transcriptome profiling can reveal prognostic biomarkers and therapeutic vulnerabilities for directing clinical care. Currently, there are no biomarkers that can accurately predict patient prognosis regarding tumor growth and the tumor immune microenvironment in vestibular schwannomas. This study aimed to investigate the mechanisms of tumor growth using bulk RNA-seq and single-cell data from patients with vestibular schwannomas. : Gene set variation analysis was used to assess groups with high and low tumor growth using four cohorts of bulk RNA-seq data (210 patients with vestibular schwannoma), 33,081 single cells, and 558 tumor growth-related genes. : SIG558, a tumor growth signature gene, was enriched in Schwann cells and microglial cells with high stemness, according to stemness analysis and cell-cell communication analysis of 33,081 single cells. We identified 391 genes that were strongly expressed in Schwann cells with high stemness. In addition, we identified 23 genes related to signal transduction that are important for tumor growth through cell-cell interactions in seven cell types at the single-cell level. : Our research demonstrates that the 23 signature genes are potential predictors and prognostic biomarkers for direct medical therapy in patients with vestibular schwannoma, and that they should be prospectively verified using large patient cohorts. These results could potentially be used in precision medicine to develop treatment strategies for vestibular schwannomas by targeting these 23 genes.

摘要

转录组分析可以揭示用于指导临床治疗的预后生物标志物和治疗易损性。目前,尚无生物标志物能够准确预测前庭神经鞘瘤患者在肿瘤生长和肿瘤免疫微环境方面的预后。本研究旨在利用前庭神经鞘瘤患者的批量RNA测序和单细胞数据来研究肿瘤生长的机制。:使用四组批量RNA测序数据(210例前庭神经鞘瘤患者)、33081个单细胞和558个与肿瘤生长相关的基因,通过基因集变异分析来评估肿瘤生长高和低的组。:根据对33081个单细胞的干性分析和细胞间通讯分析,肿瘤生长特征基因SIG558在前庭神经鞘瘤细胞和具有高干性的小胶质细胞中富集。我们鉴定出391个在前庭神经鞘瘤细胞中高表达的基因。此外,我们在单细胞水平上鉴定出23个与信号转导相关的基因,这些基因通过七种细胞类型中的细胞间相互作用对肿瘤生长很重要。:我们的研究表明,这23个特征基因是前庭神经鞘瘤患者直接药物治疗的潜在预测指标和预后生物标志物,应该使用大型患者队列进行前瞻性验证。这些结果可能会用于精准医学,通过靶向这23个基因来制定前庭神经鞘瘤的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4270/11674088/3b78dec55cd7/cancers-16-04134-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4270/11674088/62fc81a8cab0/cancers-16-04134-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4270/11674088/1c2bdf07857d/cancers-16-04134-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4270/11674088/edee4001e9a0/cancers-16-04134-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4270/11674088/3b78dec55cd7/cancers-16-04134-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4270/11674088/62fc81a8cab0/cancers-16-04134-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4270/11674088/1c2bdf07857d/cancers-16-04134-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4270/11674088/edee4001e9a0/cancers-16-04134-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4270/11674088/3b78dec55cd7/cancers-16-04134-g004.jpg

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本文引用的文献

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Neuro Oncol. 2024 Mar 4;26(3):444-457. doi: 10.1093/neuonc/noad201.
2
Single-cell sequencing reveals the cell map and transcriptional network of sporadic vestibular schwannoma.单细胞测序揭示散发型前庭神经鞘瘤的细胞图谱和转录网络。
Front Mol Neurosci. 2022 Oct 11;15:984529. doi: 10.3389/fnmol.2022.984529. eCollection 2022.
3
Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology.
独特的免疫特征可预测前庭神经鞘瘤的进展,并揭示其可能的病毒病因。
J Exp Clin Cancer Res. 2022 Oct 4;41(1):292. doi: 10.1186/s13046-022-02473-4.
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Vestibular Schwannoma Volume and Tumor Growth Correlates with Macrophage Marker Expression.前庭神经鞘瘤体积与肿瘤生长与巨噬细胞标志物表达相关。
Cancers (Basel). 2022 Sep 12;14(18):4429. doi: 10.3390/cancers14184429.
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Single-Cell RNA-Seq Reveals Heterogeneity of Cell Communications between Schwann Cells and Fibroblasts within Vestibular Schwannoma Microenvironment.单细胞 RNA 测序揭示了前庭神经鞘瘤微环境中施万细胞与成纤维细胞之间细胞通讯的异质性。
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