探讨膀胱癌中 costimulatory 基因的预后作用

IF 3.2 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Gene Medicine Pub Date : 2024-01-06 DOI:10.1002/jgm.3655
Hao Su, Ziqi Liu, Chaoyue Zhang, Zebin Deng, Xiaozhe Su, Yinhuai Wang, Wentao Liu
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引用次数: 0

摘要

背景 基于成本刺激分子构建膀胱癌预后模型,并在不同数据集中验证其稳定性和准确性。 方法 利用计算生物学方法分析了癌症基因组图谱(TCGA)数据库中膀胱癌 RNA 的表达谱和相应的临床数据,并构建了成本刺激分子相关基因的预后模型。该模型应用于 TCGA 数据集和基因表达总库数据库中的 GSE160693、GSE176307、Xiangya_Cohort、GSE13507、GSE19423、GSE31684、GSE32894、GSE48075、GSE69795 和 GSE70691。研究还探讨了成本刺激分子在膀胱癌肿瘤亚型中的作用。通过一致聚类分析,TCGA 数据集中的膀胱癌被分为两个亚型:C1和C2。C1 亚型预后较差,免疫细胞浸润程度高,自然杀伤细胞、T 细胞和树突状细胞在 C1 亚型中明显富集。此外,ESTIMATE 算法计算出的 ImmuneScore 在两个亚型之间存在很大差异,C1 亚型的 ImmuneScore 明显高于 C2 亚型。 结果 这项研究还评估了成本刺激分子与免疫疗法反应之间的关系。高风险组对免疫疗法的反应较差,两组大多数免疫细胞的数量存在显著差异。此外,ESTIMATE 算法的三个指数和 CIBERSORT 算法的 22 个免疫细胞与风险值显著相关。这些发现表明,成本刺激分子在预测免疫疗法反应方面具有潜在价值。 结论 建立了基于成本刺激分子的膀胱癌预后模型,并通过多个数据集进行了验证。该模型为针对每个膀胱癌患者量身定制治疗方案提供了一种新模式,并为临床选择提供了有价值的见解。同时,这项研究还深入探讨了成本刺激分子在不同膀胱癌亚型中的意义,为改进膀胱癌治疗的免疫疗法策略提供了新的见解。
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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Exploration of the prognostic effect of costimulatory genes in bladder cancer

Background

A prognostic model of bladder cancer was constructed based on costimulatory molecules, and its stability and accuracy were verified in different datasets.

Method

The expression profile of bladder cancer RNA and the corresponding clinical data in The Cancer Genome Atlas (TCGA) database were analyzed employing computational biology, and a prognostic model was constructed for costimulating molecule-related genes. The model was applied in GSE160693, GSE176307, Xiangya_Cohort, GSE13507, GSE19423, GSE31684, GSE32894, GSE48075, GSE69795 and GSE70691 in TCGA dataset and Gene Expression Omnibus database. The role of costimulating molecules in bladder cancer tumor subtypes was also explored. By consistent cluster analysis, bladder cancer in the TCGA dataset was categorized into two subtypes: C1 and C2. The C1 subtype exhibited a poor prognosis, high levels of immune cell infiltration and significant enrichment of natural killer cells, T cells and dendritic cells in the C1 subtype. In addition, the ImmuneScore calculated by the ESTIMATE algorithm differed greatly between the two subtypes, and the ImmuneScore of the C1 subtype was greater than the C2 subtype in a significant manner.

Results

This study also assessed the relationship between costimulating molecules and immunotherapy response. The high-risk group responded poorly to immunotherapy, with significant differences in the amount of most immune cells between the two groups. Further, three indices of the ESTIMATE algorithm and 22 immune cells of the CIBERSORT algorithm were significantly correlated with risk values. These findings suggest the potential value of costimulating molecules in predicting immunotherapy response.

Conclusion

A costimulatory molecule-based prognostic model for bladder cancer was established and validated across multiple datasets. This model introduces a novel mode for tailoring treatments to each individual with bladder cancer, and offers valuable insights for informed clinical choices. Simultaneously, this research also delved into the significance of costimulating molecules within distinct bladder cancer subtypes, shedding novel insights into improving immunotherapy strategies for the treatment of bladder cancer.

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来源期刊
Journal of Gene Medicine
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
80
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.
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