Oxidative phosphorylation-related genes for prognosis and tumor microenvironment in breast cancer.

IF 1.7 4区医学 Q4 ONCOLOGY Translational cancer research Pub Date : 2025-01-31 Epub Date: 2025-01-23 DOI:10.21037/tcr-24-1181

Man-Zhi Xia, Shu-Feng Dong, Chun-Lei Wang

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Abstract

Background: Oxidative phosphorylation (OXPHOS) is a major energy resource occurring in mitochondria. Targeting OXPHOS-related genes has emerged as potential targets for cancer therapy. This study aimed to explore the significance of OXPHOS-related genes in breast cancer (BRCA).

Methods: Differentially expressed genes (DEGs) related to OXPHOS in BRCA were identified using packages of Limma and VennDiagram using the data from public databases. A prognostic model based on differentially expressed OXPHOS-related genes was constructed using least absolute shrinkage and selection operator Cox regression analyses and then evaluated through Kaplan-Meier and receiver operator characteristic (ROC) curves. Additionally, gene set variate analysis (GSVA) and gene set enrichment analysis (GSEA) were performed to explore the potential pathways involved in BRCA. Furthermore, the tumor microenvironment (TME) difference between low- and high-risk BRCA groups was investigated. The prognostic significance of hub genes was then examined. We conducted a protein-protein interaction (PPI) network to uncover the potential gene interactions and identify key genes, whose expressions were validated in cells.

Results: Our analyses revealed 234 differentially expressed OXPHOS-related genes, from which a nine-gene (ATP5PF, FOXP3, IGF2, IREB2, MIEF2, NOTCH1, PDE12, SHC1, and UCP3) prognostic model was constructed. Patients in the high-risk group exhibited poorer survival outcomes and a suppressed immune microenvironment compared to the low-risk group. Additionally, except for IGF2, abnormal expression levels of hub genes were significantly associated with poor prognosis of BRCA patients. GSVA and GSEA highlighted the involvement of TME-related pathways, such as transforming growth factor beta (TGF-β) and mechanistic target of rapamycin (mTOR) signaling pathways. PPI network identified 4 common genes that interacted with all hub genes. The in vitro experiment on the key genes showed a consistent result with the bioinformatics finding.

Conclusions: Our study provides insights into the prognostic biomarkers and molecular mechanisms in BRCA, offering potential therapeutic avenues and guiding personalized treatment strategies for improved patient outcomes.

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氧化磷酸化相关基因对乳腺癌预后和肿瘤微环境的影响。

背景：氧化磷酸化（OXPHOS）是发生在线粒体中的主要能量来源。靶向oxphos相关基因已成为癌症治疗的潜在靶点。本研究旨在探讨oxphos相关基因在乳腺癌（BRCA）中的意义。方法：使用Limma和VennDiagram软件，利用公共数据库数据，鉴定BRCA中与OXPHOS相关的差异表达基因（DEGs）。采用最小绝对收缩和选择算子Cox回归分析构建基于差异表达的oxphos相关基因的预后模型，并通过Kaplan-Meier曲线和receiver operator characteristic （ROC）曲线进行评估。此外，我们还进行了基因集变量分析（GSVA）和基因集富集分析（GSEA）来探索BRCA的潜在通路。此外，我们还研究了低、高风险BRCA组之间肿瘤微环境（TME）的差异。然后检查中枢基因的预后意义。我们通过蛋白-蛋白相互作用（PPI）网络揭示了潜在的基因相互作用，并鉴定了关键基因，其表达在细胞中得到了验证。结果：我们分析了234个差异表达的oxphos相关基因，并由此构建了9个基因（ATP5PF、FOXP3、IGF2、IREB2、MIEF2、NOTCH1、PDE12、SHC1和UCP3）的预后模型。与低风险组相比，高危组患者表现出较差的生存结果和抑制的免疫微环境。此外，除IGF2外，hub基因的异常表达水平与BRCA患者预后不良显著相关。GSVA和GSEA强调了tme相关通路的参与，如转化生长因子β (TGF-β)和雷帕霉素（mTOR）信号通路。PPI网络鉴定出4个与所有枢纽基因相互作用的共同基因。关键基因的体外实验结果与生物信息学研究结果一致。结论：我们的研究为BRCA的预后生物标志物和分子机制提供了见解，为改善患者预后提供了潜在的治疗途径和指导个性化治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational cancer research ONCOLOGY-

CiteScore

2.10

自引率

0.00%

发文量

252

期刊介绍： Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.