Polyamine metabolism and immune related genes as prognostic features in breast cancer: a novel risk model approach.

IF 1.7 4区 医学 Q4 ONCOLOGY
Translational cancer research Pub Date : 2025-06-30 Epub Date: 2025-06-26 DOI:10.21037/tcr-2024-2505
Weimiao Li, Changyou Shan, Liang Liang, Guoxu Zheng, Shuqun Zhang
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引用次数: 0

Abstract

Background: The biological role of polyamine metabolism-related genes (PMRGs) in breast cancer (BRCA) through immune mediation is not well understood. Consequently, this study aimed to explore the prognostic features connected to PMRGs and immune-related genes (IRGs) in BRCA via bioinformatics analysis.

Methods: We analyzed The Cancer Genome Atlas (TCGA)-BRCA and GSE20685 datasets. Differential expression analysis revealed differentially expressed genes (DEGs) in TCGA-BRCA, which intersected with 1,793 IRGs and 59 PMRGs to identify candidate genes. A least absolute shrinkage and selection operator (LASSO) Cox regression model was used to screen prognostic genes, which were then used to develop a risk model. This model was validated in both datasets. A nomogram was constructed using independent prognostic factors from univariate and multivariate Cox regression analyses to predict BRCA patient survival. The immune microenvironment landscape and gene set enrichment analysis (GSEA) results were also characterized.

Results: Among 9,558 DEGs, 1,793 IRGs, and 59 PMRGs, 10 candidate genes were identified, with PSME2, PSMB8, and PSMD14 selected as prognostic genes. The risk model stratified BRCA patients into high- and low-risk groups, with high-risk patients showing worse survival according to Kaplan-Meier analysis. The nomogram, which is based on the pathological stage and risk score, accurately predicts patient viability. High-risk patients have poor immune responses. GSEA revealed immune-related pathway involvement. PSME2 and PSMB8 were upregulated in the control samples, whereas PSMD14 was increased in the BRCA samples. The CCK8 assay results indicated that PSMD14 significantly promotes the proliferation of BRCA cells.

Conclusions: PMRGs and IRGs, specifically PSME2, PSMB8, and PSMD14, are potential prognostic markers in BRCA. A risk model and nomogram based on these genes were developed to assess BRCA prognosis effectively. These tools can improve the prognostic assessment of BRCA patients.

多胺代谢和免疫相关基因作为乳腺癌的预后特征:一种新的风险模型方法。
背景:多胺代谢相关基因(PMRGs)在乳腺癌(BRCA)中通过免疫介导的生物学作用尚不清楚。因此,本研究旨在通过生物信息学分析探讨与BRCA中PMRGs和免疫相关基因(IRGs)相关的预后特征。方法:我们分析了癌症基因组图谱(TCGA)-BRCA和GSE20685数据集。差异表达分析显示,TCGA-BRCA中存在差异表达基因(DEGs),这些基因与1793个IRGs和59个PMRGs相交,以确定候选基因。最小绝对收缩和选择算子(LASSO) Cox回归模型用于筛选预后基因,然后用于建立风险模型。该模型在两个数据集中都得到了验证。利用单因素和多因素Cox回归分析的独立预后因素构建nomogram来预测BRCA患者的生存。免疫微环境景观和基因集富集分析(GSEA)结果也进行了表征。结果:在9558个deg、1793个IRGs和59个PMRGs中,鉴定出10个候选基因,其中PSME2、PSMB8和PSMD14被选为预后基因。风险模型将BRCA患者分为高危组和低危组,根据Kaplan-Meier分析,高危患者生存率较差。nomogram nomogram nomogram nomogram nomogram nomogram nomogram nomogram病理分期和风险评分nomogram生存能力nomogram生存能力nomogram生存能力nomogram生存能力nomogram生存能力nomogram高危患者免疫反应较差。GSEA显示免疫相关通路参与。在对照样本中,PSME2和PSMB8表达上调,而在BRCA样本中,PSMD14表达上调。CCK8实验结果显示PSMD14显著促进BRCA细胞的增殖。结论:PMRGs和IRGs,特别是PSME2、PSMB8和PSMD14,是BRCA的潜在预后标志物。建立了基于这些基因的风险模型和nomogram来有效评估BRCA预后。这些工具可以改善BRCA患者的预后评估。
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来源期刊
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.
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