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鉴定与乳腺癌临床和预后特征相关的新型免疫铁死亡相关基因。

Identification of novel immune ferroptosis-related genes associated with clinical and prognostic features in breast cancer.

作者信息

Xie Zhenlan, Li Jialin, Liu Chen, Zhao Tie, Xing Yixiang

机构信息

Department of Pathology, Tongling People's Hospital, Tongling, China.

Tongling Vocational and Technical College, Tongling, China.

出版信息

Front Genet. 2023 Apr 12;14:1173159. doi: 10.3389/fgene.2023.1173159. eCollection 2023.

Abstract

Breast cancer is the most common form of cancer among women, it is critical to identify potential targets and prognostic biomarkers. Ferroptosis combined with immunity shows a pivotal role in a variety of tumors, which provides new opportunities to detect and treat breast cancer. Our first step was to combine multiple datasets to search for immune ferroptosis-related mRNAs. In the next step, risk signatures were created using Least Absolute Shrinkage and Selection Operator (LASSO). After that, based on the results of the multivariate Cox analysis, we created a prognostic nomogram and validated the model's accuracy. Finally, functional enrichment analysis, single sample gene set enrichment analysis (ssGSEA), immunity and drug sensitivity correlation analysis were performed to explore the possible mechanisms by which these immune ferroptosis associated mRNAs affect BRCA survival. An immune ferroptosis signature (IFRSig) consisting of 5 mRNAs was constructed and showed excellent predictability in the training and validation cohorts. A correlation analysis revealed that clinical characteristics were closely related to risk characteristics. Our nomogram model, which we created by combining risk characteristics and clinical parameters, was proven to be accurate at predicting BRCA prognosis. Further, we divided patients into lowrisk and high-risk groups based on the expression of the model-related genes. Compared with low-risk group, high-risk group showed lower levels of immune cell infiltration, immune-related functions, and immune checkpoints molecules, which may associate with the poor prognosis. The IFRSig could be used to predict overall survival (OS) and treatment response in BRCA patients and could be viewed as an independent prognostic factor. The findings in this study shed light on the role of immune ferroptosis in the progression of BRCA.

摘要

乳腺癌是女性中最常见的癌症形式,识别潜在靶点和预后生物标志物至关重要。铁死亡与免疫相结合在多种肿瘤中发挥关键作用,这为乳腺癌的检测和治疗提供了新机会。我们的第一步是合并多个数据集以搜索免疫铁死亡相关的mRNA。下一步,使用最小绝对收缩和选择算子(LASSO)创建风险特征。之后,基于多变量Cox分析的结果,我们创建了一个预后列线图并验证了模型的准确性。最后,进行功能富集分析、单样本基因集富集分析(ssGSEA)、免疫与药物敏感性相关性分析,以探索这些免疫铁死亡相关mRNA影响乳腺癌生存的可能机制。构建了一个由5个mRNA组成的免疫铁死亡特征(IFRSig),并在训练和验证队列中显示出优异的预测能力。相关性分析表明临床特征与风险特征密切相关。我们通过结合风险特征和临床参数创建的列线图模型被证明在预测乳腺癌预后方面是准确的。此外,我们根据模型相关基因的表达将患者分为低风险和高风险组。与低风险组相比,高风险组的免疫细胞浸润、免疫相关功能和免疫检查点分子水平较低,这可能与预后不良有关。IFRSig可用于预测乳腺癌患者的总生存期(OS)和治疗反应,并可被视为一个独立的预后因素。本研究的结果揭示了免疫铁死亡在乳腺癌进展中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e94e/10132627/cc10cc91c23d/fgene-14-1173159-g001.jpg

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