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氧化应激相关基因评分可预测乳腺癌的预后及免疫细胞浸润格局特征。

Oxidative stress-related genes score predicts prognosis and immune cell infiltration landscape characterization in breast cancer.

作者信息

Liu Diya, Fang Lin

机构信息

Department of Thyroid and Breast Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.

出版信息

Heliyon. 2024 Jul 4;10(13):e34046. doi: 10.1016/j.heliyon.2024.e34046. eCollection 2024 Jul 15.

Abstract

BACKGROUND

The tumor microenvironment (TME) typically experiences oxidative stress (OS), marked by a high level of reactive oxygen species (ROS) that can impact tumor advancement and prognosis by modulating the behavior of tumor cells and various immune cells. Oxidative stress-related genes (OSRG) encompass a range of genes involved in ROS pathways, and their specific roles in breast cancer (BC) necessitate further investigation.

METHODS

Univariate Cox analysis was performed on genes linked to the OS pathway in the Gene Set Enrichment Analysis (GSEA) database, leading to the identification of 29 significant OSRG in BC. OSRG was divided into three distinct clusters according to the expression and the OSRG score based on the differentially expressed genes (DEGs) was further calculated by principal component analysis (PCA). The correlation between OSRG score and BC clinical features, mutation characteristics, immune checkpoints and immune cell infiltration was analyzed. Establish a multiariable Cox regression model to predict OSRG score effects on clinical characteristics.

RESULTS

Significant differences were observed in survival analysis, enriched pathways, and immune infiltration among the three OSRG clusters based on 29 genes. Gene clusters were identified through the final selected 395 DEGs, revealing three distinct OSRG expression patterns. An OSRG score model was constructed using DEGs, demonstrating a significant association between high OSRG score and poor prognosis. Significantly, immune checkpoint-related genes exhibited a notable upregulation in the high OSRG score cohort. Additionally, a positive correlation was observed between the OSRG score and tumor mutation burden (TMB) in BC. The OSRG score holds potential implications for clinical immunotherapy in BC patients, and a nomogram was constructed with robust predictive capability for evaluating patient prognosis.

CONCLUSIONS

This study elucidated the features of OSRG within BC TME and their possible prognostic significance, offering valuable insights for the development of more targeted immunotherapy approaches for individuals with BC.

摘要

背景

肿瘤微环境(TME)通常会经历氧化应激(OS),其特征是高水平的活性氧(ROS),ROS可通过调节肿瘤细胞和各种免疫细胞的行为来影响肿瘤进展和预后。氧化应激相关基因(OSRG)包括一系列参与ROS通路的基因,其在乳腺癌(BC)中的具体作用需要进一步研究。

方法

对基因集富集分析(GSEA)数据库中与OS通路相关的基因进行单变量Cox分析,从而在BC中鉴定出29个显著的OSRG。根据表达情况将OSRG分为三个不同的簇,并通过主成分分析(PCA)进一步计算基于差异表达基因(DEG)的OSRG评分。分析OSRG评分与BC临床特征、突变特征、免疫检查点和免疫细胞浸润之间的相关性。建立多变量Cox回归模型以预测OSRG评分对临床特征的影响。

结果

基于29个基因的三个OSRG簇在生存分析、富集通路和免疫浸润方面存在显著差异。通过最终选定的395个DEG鉴定出基因簇,揭示了三种不同的OSRG表达模式。使用DEG构建了OSRG评分模型,结果表明高OSRG评分与不良预后之间存在显著关联。值得注意的是,免疫检查点相关基因在高OSRG评分队列中显著上调。此外,在BC中观察到OSRG评分与肿瘤突变负荷(TMB)之间呈正相关。OSRG评分对BC患者的临床免疫治疗具有潜在意义,并构建了具有强大预测能力的列线图以评估患者预后。

结论

本研究阐明了BC-TME中OSRG的特征及其可能的预后意义,为开发更具针对性的BC个体免疫治疗方法提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d1/11283013/6cbf71e4b229/gr1.jpg

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