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铁死亡在乳腺癌患者中的作用:一项综合分析。

The role of ferroptosis in breast cancer patients: a comprehensive analysis.

作者信息

Wu Zeng-Hong, Tang Yun, Yu Hong, Li Hua-Dong

机构信息

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.

出版信息

Cell Death Discov. 2021 May 4;7(1):93. doi: 10.1038/s41420-021-00473-5.

Abstract

Breast cancer (BC) affects the breast tissue and is the second most common cause of mortalities among women. Ferroptosis is an iron-dependent cell death mode that is characterized by intracellular accumulation of reactive oxygen species (ROS). We constructed a prognostic multigene signature based on ferroptosis-associated differentially expressed genes (DEGs). Moreover, we comprehensively analyzed the role of ferroptosis-associated miRNAs, lncRNAs, and immune responses. A total of 259 ferroptosis-related genes were extracted. KEGG function analysis of these genes revealed that they were mainly enriched in the HIF-1 signaling pathway, NOD-like receptor signaling pathway, central carbon metabolism in cancer, and PPAR signaling pathway. Fifteen differentially expressed genes (ALOX15, ALOX15B, ANO6, BRD4, CISD1, DRD5, FLT3, G6PD, IFNG, NGB, NOS2, PROM2, SLC1A4, SLC38A1, and TP63) were selected as independent prognostic factors for BC patients. Moreover, T cell functions, including the CCR score, immune checkpoint, cytolytic activity, HLA, inflammation promotion, para-inflammation, T cell co-stimulation, T cell co-inhibition, and type II INF responses were significantly different between the low-risk and high-risk groups of the TCGA cohort. Immune checkpoints between the two groups revealed that the expressions of PDCD-1 (PD-1), CTLA4, LAG3, TNFSF4/14, TNFRSF4/8/9/14/18/25, and IDO1/2 among others were significantly different. A total of 1185 ferroptosis-related lncRNAs and 219 ferroptosis-related miRNAs were also included in this study. From the online database, we identified novel ferroptosis-related biomarkers for breast cancer prognosis. The findings of this study provide new insights into the development of new reliable and accurate cancer treatment options.

摘要

乳腺癌(BC)会影响乳腺组织,是女性死亡的第二大常见原因。铁死亡是一种铁依赖性细胞死亡模式,其特征是细胞内活性氧(ROS)积累。我们基于铁死亡相关差异表达基因(DEG)构建了一个预后多基因特征。此外,我们全面分析了铁死亡相关miRNA、lncRNA和免疫反应的作用。共提取了259个铁死亡相关基因。对这些基因的KEGG功能分析表明,它们主要富集在缺氧诱导因子-1(HIF-1)信号通路、NOD样受体信号通路、癌症中的中心碳代谢和过氧化物酶体增殖物激活受体(PPAR)信号通路。选择15个差异表达基因(15-脂氧合酶15,15-脂氧合酶15B,ANO6,溴结构域蛋白4,含硒蛋白1,多巴胺受体D5,FMS样酪氨酸激酶3,葡萄糖-6-磷酸脱氢酶,干扰素γ,神经球蛋白,一氧化氮合酶2,prominin-2,溶质载体家族1成员4,溶质载体家族38成员1和肿瘤蛋白p63)作为BC患者的独立预后因素。此外,TCGA队列的低风险和高风险组之间的T细胞功能,包括CCR评分、免疫检查点、细胞溶解活性、人类白细胞抗原(HLA)、炎症促进、类炎症、T细胞共刺激、T细胞共抑制和II型干扰素反应存在显著差异。两组之间的免疫检查点显示,程序性死亡受体1(PD-1)、细胞毒性T淋巴细胞相关蛋白4(CTLA4)、淋巴细胞活化基因3蛋白(LAG3)、肿瘤坏死因子配体超家族成员4/14(TNFSF4/14)、肿瘤坏死因子受体超家族成员4/8/9/14/18/25以及吲哚胺2,3-双加氧酶1/2(IDO1/2)等的表达存在显著差异。本研究还纳入了1185个铁死亡相关lncRNA和219个铁死亡相关miRNA。通过在线数据库,我们确定了用于乳腺癌预后的新型铁死亡相关生物标志物。本研究结果为开发新的可靠且准确的癌症治疗方案提供了新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a0/8097021/09cf09ae4096/41420_2021_473_Fig1_HTML.jpg

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