Cuproptosis-related classification and personalized treatment in lower-grade gliomas to prompt precise oncology

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2023-02-22 DOI:10.1002/jgm.3486

Nanxi Shen, Shu Chen, Dong Liu, Xiangde Min, Qinghai Tan

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引用次数: 2

Abstract

Background

Cuproptosis is implicated in regulating tricarboxylic acid cycle and associated with tumor therapeutic sensitivity, patient outcomes and tumorigenesis. However, the classification and prognostic effect of cuproptosis-associated genes (CAGs), the relationship between cuproptosis and tumor microenvironment (TME) and the treatment of lower-grade glioma (LrGG) remain enigmatic.

Methods

The genetic and transcriptional alterations, prognostic value and classification related to cuproptosis were systematically analyzed. Subtypes of cuproptosis and cuproptosis score (Cuscore) were constructed and further confirmed by two external cohorts. The relationships between cuproptosis and TME, prognosis, and treatment response were also evaluated.

Results

Four clusters were identified based on cuproptosis-associated genes. The associations between cuproptosis-associated clusters and clinical features, prognosis, immune cell infiltration, and chemotherapy sensitivity were observed. The Cuscore is an independent prognostic indicator in LrGG patients. The nomogram is constructed according to Cuscore and clinical characteristics, and has good predictive ability and calibration. Patients with high Cuscore had a worse prognosis and advanced performance. A higher Cuscore also indicated a higher stromal score, abundant immune infiltration, and increased tumor mutation burden. A high Cuscore was remarkably related to immune checkpoint inhibitors, immunotherapy response and immune phenotype.

Conclusions

This study demonstrates the clinical effect of CAGs, and suggests that cuproptosis could be a potential therapeutic target in LrGG.

Abstract Image

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低度胶质瘤中铜裂相关的分类和个体化治疗以促进精确的肿瘤学

背景cuprotosis参与调节三羧酸循环，并与肿瘤治疗敏感性、患者预后和肿瘤发生有关。然而，铜凸相关基因(CAGs)的分类和预后作用、铜凸与肿瘤微环境(TME)的关系以及低级别胶质瘤(LrGG)的治疗仍然是一个谜。方法系统分析铜骨畸形的遗传和转录改变、预后价值及分类。构建铜凸和铜凸评分(Cuscore)亚型，并通过两个外部队列进一步证实。并对畸形与TME、预后及治疗效果的关系进行了评价。结果根据铜裂病相关基因鉴定出4个聚类。观察铜腐病相关簇与临床特征、预后、免疫细胞浸润和化疗敏感性的关系。Cuscore是LrGG患者的独立预后指标。根据Cuscore和临床特征构建nomogram，具有良好的预测能力和校准能力。高Cuscore患者预后较差，预后较差。Cuscore越高，间质评分越高，免疫浸润丰富，肿瘤突变负担加重。高Cuscore与免疫检查点抑制剂、免疫治疗反应和免疫表型显著相关。结论本研究证实了CAGs的临床效果，提示铜凸可能是LrGG的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.