A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer.
A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer.
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DOI：
10.3389/fmolb.2021.678877
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发表时间：
2021
影响因子：
5
通讯作者：
Tang J
中科院分区：
文献类型：
--
作者：
Zhang K;Ping L;Du T;Liang G;Huang Y;Li Z;Deng R;Tang J
背景：铁凋亡是一种受铁依赖性脂质过氧化作用驱动的细胞死亡，在癌症中起重要作用。然而，关于乳腺癌中凋亡相关的长链非编码rna （Long non-coding RNAs, lncRNAs）的研究有限。此外，凋亡相关lncrna在乳腺癌中的预后作用及其与免疫微环境的关系尚不清楚。本研究旨在探讨凋亡相关lncrna在乳腺癌中的潜在预后价值及其与免疫微环境的关系。方法：从TCGA数据库下载女性乳腺癌患者的rna测序数据。937例患者按2:1的比例随机分为训练组和验证组。通过Pearson相关分析筛选239个已报道的嗜铁相关基因。在训练队列中，通过单因素和多因素Cox回归分析构建了与铁衰相关的lncrna特征，并在验证队列中进一步检验其预后价值。结果：通过多因素Cox回归分析，建立了8-铁中毒相关lncrnas特征，将患者分为两个风险组。高危组患者预后较低危组患者差。多因素Cox回归分析显示，风险评分是独立的预后指标。受试者工作特征曲线（ROC）分析证明了该特征的预测准确性。训练组1年、2年、5年ROC曲线下面积（AUC）分别为0.853、0.802、0.740，验证组1年、2年、5年分别为0.791、0.778、0.722。进一步分析表明，免疫相关通路在高危组中显著富集。免疫细胞浸润景观分析显示，乳腺癌高危人群在免疫上趋向“冷”。结论：我们发现了一个新的与嗜铁性凋亡相关的lncRNA特征，可以准确预测乳腺癌患者的预后。凋亡相关lncrna可能在抗肿瘤免疫过程中具有潜在的作用，可作为乳腺癌的治疗靶点。
Background: Ferroptosis, a regulated cell death which is driven by the iron-dependent peroxidation of lipids, plays an important role in cancer. However, studies about ferroptosis-related Long non-coding RNAs (lncRNAs) in breast cancer (BC) are limited. Besides, the prognostic role of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer remain unclear. This study aimed to explore the potential prognostic value of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer. Methods: RNA-sequencing data of female breast cancer patients were downloaded from TCGA database. 937 patients were randomly separated into training or validation cohort in 2:1 ratio. Ferroptosis-related lncRNAs were screened by Pearson correlation analysis with 239 reported ferroptosis-related genes. A ferroptosis-related lncRNAs signature was constructed with univariate and multivariate Cox regression analyses in the training cohort, and its prognostic value was further tested in the validation cohort. Results: An 8-ferroptosis-related-lncRNAs signature was developed by multivariate Cox regression analysis to divide patients into two risk groups. Patients in the high-risk group had worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed the risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The area under time-dependent ROC curve (AUC) reached 0.853 at 1 year, 0.802 at 2 years, 0.740 at 5 years in the training cohort and 0.791 at 1 year, 0.778 at 2 years, 0.722 at 5 years in the validation cohort. Further analysis demonstrated that immune-related pathways were significantly enriched in the high-risk group. Analysis of the immune cell infiltration landscape showed that breast cancer in the high-risk group tended be immunologically “cold”. Conclusion: We identified a novel ferroptosis-related lncRNA signature which could precisely predict the prognosis of breast cancer patients. Ferroptosis-related lncRNAs may have a potential role in the process of anti-tumor immunity and serve as therapeutic targets for breast cancer.