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一种新型铁死亡相关长非编码 RNA 标志物用于预测乳腺癌患者无复发生存。

A novel ferroptosis-related long noncoding RNA signature for relapse free survival prediction in patients with breast cancer.

机构信息

Department of Laboratory Medicine, People's Hospital of Deyang City, Deyang, Sichuan, P. R. China.

Department of Laboratory Medicine, Chengdu Women's and Children's Central Hospital, Chengdu, Sichuan, P. R. China.

出版信息

Medicine (Baltimore). 2022 Aug 5;101(31):e29573. doi: 10.1097/MD.0000000000029573.

Abstract

Ferroptosis is the process of cell death dependent on iron. Growing evidence suggests that ferroptosis plays vital roles in the biological process of many cancers. However, just a small number of ferroptosis-related lncRNAs have been explored in depth. Ferroptosis-related lncRNAs in breast cancer (BC) were identified by co-expression analysis based on The Cancer Genome Atlas database (TCGA). The whole set was divided into a training set and a test set with a 1:1 ratio. Univariate Cox regression and LASSO analyses were performed to establish a signature in the 3 sets. Kaplan-Meier analysis and receiver operating characteristic (ROC) for the 3 sets validated the effectiveness and robustness of the signature. Besides, we also explore the relationship between this and clinical characteristics, immune cell infiltration and tumor microenvironment. Meanwhile, the nomogram was drawn by screening indicators of independent recurrent prediction. Finally, we evaluated the relationships between the signature and tumor microenvironment. We identified 391 ferroptosis-related lncRNAs and constructed a 5 lncRNAs-based signature in the training, test, and whole sets, stratifying patients into high-risk and low-risk groups. According to survival analysis, patients in the high-risk groups had worse relapse free survival (RFS) compared to the low risk-groups. The ROC curves indicated that the recurrent signature had a promising predictive capability for BC patients. Moreover, an independent factors-based nomogram model could offer the quantitative prediction and net benefit for the recurrence of BC patients. Finally, the microenvironment, including tumor mutational burden (TMB), immune cell functions and immune checkpoints, showed big differences between the 2 groups. The 5 ferroptosis-related lncRNAs and their signature might be novel promising biomarkers and immunotherapy targets for patients with BC.

摘要

铁死亡是一种依赖于铁的细胞死亡过程。越来越多的证据表明,铁死亡在许多癌症的生物学过程中起着至关重要的作用。然而,只有少数铁死亡相关的长链非编码 RNA 被深入研究。通过基于癌症基因组图谱数据库(TCGA)的共表达分析,鉴定了乳腺癌(BC)中的铁死亡相关 lncRNA。整个数据集被分为 1:1 的训练集和测试集。进行单变量 Cox 回归和 LASSO 分析,以在 3 个集合中建立特征。3 个集合的 Kaplan-Meier 分析和接受者操作特征(ROC)验证了特征的有效性和稳健性。此外,我们还探讨了与临床特征、免疫细胞浸润和肿瘤微环境的关系。同时,通过筛选独立复发预测指标绘制列线图。最后,我们评估了特征与肿瘤微环境的关系。我们鉴定了 391 个铁死亡相关的 lncRNA,并在训练、测试和整个数据集构建了一个基于 5 个 lncRNA 的特征,将患者分为高危和低危组。根据生存分析,高危组患者的无复发生存(RFS)比低危组患者差。ROC 曲线表明,复发特征对 BC 患者具有良好的预测能力。此外,基于独立因素的列线图模型可以为 BC 患者的复发提供定量预测和净效益。最后,微环境,包括肿瘤突变负荷(TMB)、免疫细胞功能和免疫检查点,在两组之间显示出很大的差异。这 5 个铁死亡相关的 lncRNA 和它们的特征可能是 BC 患者新的有前途的生物标志物和免疫治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76e4/9351903/701e79791c69/medi-101-e29573-g001.jpg

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