在基底乳腺癌中,细胞外矩阵重塑和铁死之间存在不良交叉关系
Christophe Desterke1, Emma Cosialls2,3, Yao Xiang2
1UFR Médecine-INSERM UMRS1310, Université Paris-Saclay, F-94800 Villejuif, France.
Cells
|September 8, 2023
概括
这项研究通过分析铁亡和细胞外矩阵改造基因,确定了预测乳腺癌预后不佳的分子评分. 这11个基因的签名,在模型中得到验证,显示了针对性铁灭治疗的希望.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 乳腺癌是一种异质性疾病,由于转移和复发,死亡率高.
- 作为细胞死亡途径的铁灭,显示出抑制癌症生长,转移和改善治疗敏感性的潜力.
- 了解铁和瘤微环境之间的相互作用,特别是细胞外矩阵 (ECM) 重塑,至关重要.
研究的目的:
- 为了研究铁和乳腺癌中ECM重塑基因之间的关系.
- 识别与预后不佳和远程无复发生存率 (DRFS) 相关的基因特征.
- 为了验证已识别的基因特征及其通过铁灭诱导物的调节.
主要方法:
- 关于铁和ECM重塑的文献数据挖掘,与乳腺癌转录组数据集成.
- 在辅助治疗下对患者队列 (GSE25066,METABRIC) 进行远程无复发生存 (DRFS) 的分析.
- 在乳腺癌细胞系中使用铁灭激活剂 (erastin,RSL3) 的功能实验 (MDA-MB-231).
主要成果:
- 文本挖掘发现了910个与铁亡和ECM重塑相关的基因.
- 确定了11个不良基因的签名,预测了不良预后 (基底亚型,短DRFS,高等级,受体消极性,高级结节阶段).
- 这种11个基因的特征得到了验证,并被证明可以通过三阴性乳腺癌细胞中的铁灭诱导剂来调节.
结论:
- 在ECM重塑和铁化之间的交叉定义了一个分子得分,这是一个独立的不良预后参数在乳腺癌.
- 鉴定到的基因特征是由铁灭激活剂调节的,这表明了治疗潜力.
- 这种分子评分可能有助于评估乳腺癌中 Ferroptosis 向疗法的疗效.
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