揭示线粒体分裂和融合的力量:用于胃癌个性化预后的五基因特征。

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Bin Zhou, Ping Tie, Dongbing Li, You Lu, Yuanhua Liu
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引用次数: 0

摘要

背景:线粒体分裂和融合在肿瘤发生、发展和治疗中发挥着重要作用。这些过程的失调可能导致肿瘤进展,而对这些过程的调控可能为癌症治疗提供新的策略。与线粒体分裂和融合(MD)相关的基因参与胃癌(GC)的情况仍不甚明了:本研究旨在建立胃癌患者的线粒体分裂和融合基因特征,并研究其与胃癌预后、肿瘤微环境和治疗反应的关系:我们以 TCGA-GC 数据库为队列,特别关注与 MD 相关的基因。我们对MD中差异表达基因进行了鉴定和一致性聚类分析,进行了MD基因突变和拷贝数变异分析,以及MD基因簇分类与免疫浸润之间的相关性和功能富集分析。TCGA-GC 和 GSE15459 被用来构建模型的训练队列和验证队列。我们使用了多种统计方法,包括 Cox 回归和 Lasso 回归,来建立模型。我们使用批量转录组和单细胞转录组数据集(GSE13861、GSE26901、GSE66229 和 GSE13450)验证了模型。我们使用了GSEA富集、CIBERSORT算法、ESTIMATE和TIDE来深入了解MD特征的注释和肿瘤微环境的特征。我们使用 OncoPredict 分析了 PRG 特征与药物敏感性之间的关系。我们使用定量实时 PCR(qRT-PCR)技术验证了 GC 细胞系中 MD 特征中几个关键基因的表达:结果:这些与MD相关的亚型表现出不同的预后和免疫过滤模式。由 AGT、HCFC1、KIFC3、NOX4 和 RIN1 组成的五个基因特征被开发出来。低危和高危患者的总生存率有明显区别。分析表明,基因特征的独立预后价值得到了进一步证实。MD特征、免疫浸润和药物敏感性之间存在明显的相关性。AGT、HCFC1、KIFC3、NOX4和RIN1 mRNA的表达水平在这些GC细胞中均有所增加:结论:MD特征能够极大地促进个性化结果的预测,并推动为GC患者量身定制的新型治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unveiling the Power of Mitochondrial Fission and Fusion: A Five-Gene Signature for Personalized Prognosis in Gastric Cancer.

Background: Mitochondrial fission and fusion play important roles in tumorigenesis, progression and therapy. Dysregulation of these processes may lead to tumor progression, and regulation of these processes may provide novel strategies for cancer therapy. The involvement of genes related to mitochondrial fission and fusion (MD) in gastric cancer (GC) remains poorly understood.

Objective: The aim of this study was to establish an MD gene signature for GC patients and to investigate its association with prognosis, tumor microenvironment and treatment response in GC.

Methods: We use the TCGA-GC database as the cohort, focusing specifically on genes associated with MD. We conducted identification and consistency clustering analysis of differentially expressed genes in MD, conducted MD gene mutation and copy number variation analysis, as well as correlation and functional enrichment analysis between MD gene cluster classification and immune infiltration. TCGA-GC and GSE15459 were used to construct training and validation cohorts for the model. We used various statistical methods, including Cox and Lasso regression, to develop the model. We validated the model using bulk transcriptome and single- cell transcriptome datasets (GSE13861, GSE26901, GSE66229, and GSE13450). We used GSEA enrichment, CIBERSORT algorithm, ESTIMATE, and TIDE to gain insight into the annotation of MD signature and the characterization of the tumor microenvironment. OncoPredict was used to analyze the relationship between the PRG signature and the drug sensitivity. We validated the expression of several key genes in MD signature on GC cell lines using quantitative real-time PCR (qRT-PCR).

Results: These MDs-related subtypes exhibited different prognosis and immune filtration patterns. A five-gene signature, comprising AGT, HCFC1, KIFC3, NOX4, and RIN1, was developed. There was a clear distinction in overall survival between low- and high-risk patients. The analyses showed further confirmation of the independent prognostic value of the gene signature. There was a notable correlation between the MD signature, immune infiltration and drug susceptibility. The expression levels of AGT, HCFC1, KIFC3, NOX4 and RIN1 mRNA were all increased in these GC cells.

Conclusion: The MD signature has the capacity to significantly contribute to the prediction of personalized outcomes and the advancement of novel therapeutic strategies tailored for GC patients.

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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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