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振荡性缺氧诱导的基因表达预测了人类乳腺癌患者的低生存率

Yasir Suhail^1,2,3, Yamin Liu^1,3, Wenqiang Du¹

¹Department of Biomedical Engineering, University of Connecticut Health, Farmington, Connecticut, USA.

Molecular carcinogenesis

|August 16, 2024

概括

振荡性缺氧,与稳定条件不同,独特地改变了乳腺癌细胞中的基因表达. 这种动态的氧气波动驱动恶性瘤,并预测癌症患者的生存率不佳.

科学领域:

癌症生物学癌症生物学
瘤微环境瘤微环境
分子瘤学分子瘤学

背景情况:

缺氧是瘤微环境中的关键因素,影响癌症转移.
转录因子低氧诱导因子1 (HIF-1) 是细胞对低氧反应的关键调节者.
对于动态 (振荡式) 缺氧对癌症进展的影响的了解有限.

研究的目的:

为了研究在三阴性乳腺癌中由振荡性缺氧诱导的特定基因表达变化.
为了比较振荡性与稳定性低氧对癌细胞恶性瘤的影响.
为了确定在人类癌症中振荡性低氧相关基因特征的临床相关性.

主要方法:

使用了MDA-MB-231细胞,这是三阴性乳腺癌的模型,在受控的振荡性缺氧下.
测量基因表达在响应振荡性缺氧时的变化.
分析了来自人类癌症样本的癌症基因组图谱 (TCGA) RNA-seq数据.

主要成果:

与稳定的缺氧相比,振荡性缺氧会诱导不同的基因表达模式,有时会产生相反的效果.
在MDA-MB-231细胞中发现了振荡性缺氧特异性基因表达特征.
这种特征在各种人类癌症中更加丰富,并且与患者的生存率降低相关,特别是在乳腺癌中.

结论:

振荡性缺氧显著影响基因表达和癌症恶性异于稳定性缺氧.
鉴定到的振荡性缺氧基因特征是乳腺癌患者生存率差的预后标志物.
振荡性缺氧诱导了未折叠的蛋白质反应,导致生存率降低.

关键词:

在HIF-1的动态中.癌症低氧症癌症低氧症缺氧缺氧是指缺氧的情况.振荡性低氧是指振荡性低氧.不折叠的蛋白质折叠反应

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