在人类卵巢癌模型中,协调的蛋白质模块在单细胞分辨率下定义了对碳酸的DNA损伤反应
Jacob S Bedia1, Antonio Delgado-Gonzalez2, Ying-Wen Huang1
1Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell reports. Medicine
|August 23, 2025
概括
管卵巢高度血清癌 (HGSC) 对碳烯化疗的耐药性与DNA损伤反应 (DDR) 的异质性有关. 识别DDR敏感度模块可以改善这种致命的妇科恶性病的患者分层和治疗.
科学领域:
- 癌症学
- 分子生物学
- 遗传学
背景情况:
- 输卵管高度血清癌 (HGSC) 是一种致命的妇科恶性瘤.
- 对于化疗的初始反应通常会被获得抗药性.
- 抗性的机制和有效的生物标志物仍然不清楚.
研究的目的:
- 在用卡博普拉丁治疗的HGSC细胞系中研究DNA损伤反应 (DDR) 的异质性.
- 确定HGSC中碳酸耐药性的分子机制.
- 探索DDR蛋白模块作为临床分层生物标志物的潜力.
主要方法:
- 使用质量细胞计量来量化DDR蛋白质的酸化和丰度.
- 用carboplatin对待HGSC细胞系的模型.
- 使用无监督分析和矩阵分解来确定DDR状态和蛋白质模块.
主要成果:
- 尽管的吸收程度相似,但受碳白金处理的HGSC细胞表现出不同的命运,这表明DDR异质性.
- 确定了DDR状态的连续性,其中有八个不同的蛋白质模块.
- 在卡博普拉丁敏感细胞中增加了正规DDR蛋白的模块,而耐药细胞则参与了更广泛的DDR网络.
结论:
- 单细胞蛋白质组学可以有效地识别HGSC中的功能DDR状态.
- 一个特定的DDR敏感度模块显示为预测对卡博普拉丁的反应的生物标志物.
- 这些发现可以指导HGSC患者的临床分层和治疗决策.
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