Zhang Kaiming, Ping Liqin, Du Tian, Liang Gehao, Huang Yun, Li Zhiling, Deng Rong, Tang Jun
Department of Breast Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Department of Medical Oncology, State Key Laboratory of On cology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Front Mol Biosci. 2021 Jun 7;8:678877. doi: 10.3389/fmolb.2021.678877. eCollection 2021.
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. 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. 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". 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.
铁死亡是一种由铁依赖性脂质过氧化驱动的程序性细胞死亡，在癌症中起着重要作用。然而，关于乳腺癌（BC）中铁死亡相关长链非编码RNA（lncRNA）的研究有限。此外，铁死亡相关lncRNA在乳腺癌中的预后作用及其与免疫微环境的关系仍不清楚。本研究旨在探讨铁死亡相关lncRNA在乳腺癌中的潜在预后价值及其与免疫微环境的关系。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或验证组。通过与239个已报道的铁死亡相关基因进行Pearson相关分析筛选出铁死亡相关lncRNA。在训练组中通过单因素和多因素Cox回归分析构建铁死亡相关lncRNA特征，并在验证组中进一步检验其预后价值。通过多因素Cox回归分析建立了一个由8个铁死亡相关lncRNA组成的特征，将患者分为两个风险组。高风险组患者的预后比低风险组患者差。多因素Cox回归分析显示风险评分是一个独立的预后指标。受试者工作特征曲线（ROC）分析证明了该特征的预测准确性。训练组中时间依赖性ROC曲线下面积（AUC）在1年时达到0.853，2年时达到0.802，5年时达到0.740；验证组中1年时为0.791，2年时为0.778，5年时为0.722。进一步分析表明，免疫相关通路在高风险组中显著富集。免疫细胞浸润图谱分析显示，高风险组的乳腺癌倾向于免疫“冷”型。我们鉴定出一种新的铁死亡相关lncRNA特征，可精确预测乳腺癌患者的预后。铁死亡相关lncRNA可能在抗肿瘤免疫过程中发挥潜在作用，并可作为乳腺癌的治疗靶点。
