肿瘤休眠与神经母细胞瘤的预后预测及肿瘤免疫密切相关。

Tumor dormancy is closely related to prognosis prediction and tumor immunity in neuroblastoma.

作者信息

Tian Xiangdong, Cao Fuliang, Li Xin, He Yuchao, Xia Yuren, Chen Lu, Zhao Qiang

机构信息

National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

出版信息

Transl Pediatr. 2023 Mar 31;12(3):445-461. doi: 10.21037/tp-23-119. Epub 2023 Mar 30.

Abstract

BACKGROUND

Neuroblastoma (NB), which is the most frequent and fatal solid tumor in early childhood, lacks an accurate approach to prevent or forecast its recurrence. Dormant NB cells are responsible for metastasis, drug resistance, and suppressive activity in the immune system. However, there is a lack of systematic research on the interaction between dormancy and NB prognosis and its potential associations with tumor immunity.

METHODS

We downloaded NB gene expression data and clinical information from the Gene Expression Omnibus and ArrayExpres databases. Based on consensus clustering of the expression of dormancy-associated genes, the NB samples were classified into different groups, and differentially expressed genes (DEGs) were explored in each group. Functional analyses of DEGs were performed, followed by the establishment of a predictive dormancy signature and the assessment of tumor immunity. Finally, sex, age, International Neuroblastoma Staging System (INSS) stage, and status were identified as independent overall survival-related variables, which were incorporated into the nomogram.

RESULTS

A dormancy-associated gene signature, including , , , , , and was established. The gene signature showed a strong correlation with NB immune infiltration and capacity to predict NB patient prognosis. A nomogram including status, INSS stage, age and gene signature risk score was established which further divided NB into high, medium and low-risk groups. This nomogram had certain guiding significance in decision-making for clinical treatment.

CONCLUSIONS

Our results suggested that the 6-gene genetic signature for NB based on dormancy could predict NB survival and response to immunotherapy.

摘要

背景

神经母细胞瘤(NB)是儿童早期最常见且致命的实体瘤,缺乏预防或预测其复发的准确方法。休眠的NB细胞负责转移、耐药以及免疫系统中的抑制活性。然而,关于休眠与NB预后之间的相互作用及其与肿瘤免疫的潜在关联,目前缺乏系统性研究。

方法

我们从基因表达综合数据库(Gene Expression Omnibus)和ArrayExpres数据库下载了NB基因表达数据和临床信息。基于休眠相关基因表达的一致性聚类,将NB样本分为不同组,并在每组中探索差异表达基因(DEGs)。对DEGs进行功能分析,随后建立预测休眠特征并评估肿瘤免疫。最后,将性别、年龄、国际神经母细胞瘤分期系统(INSS)分期和状态确定为独立的总生存相关变量,并将其纳入列线图。

结果

建立了一个包含、、、、、和的休眠相关基因特征。该基因特征与NB免疫浸润以及预测NB患者预后的能力密切相关。建立了一个包含状态、INSS分期、年龄和基因特征风险评分的列线图,该列线图进一步将NB分为高、中、低风险组。此列线图在临床治疗决策中具有一定的指导意义。

结论

我们的结果表明,基于休眠的NB 6基因遗传特征可以预测NB的生存情况以及对免疫治疗的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/163d/10080482/234fb3ec454a/tp-12-03-445-f1.jpg

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