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来自跨癌症共享的分子相互作用的转录和蛋白质签名与死亡率有关
Yelin Zhao1, Xinxiu Li1, Joseph Loscalzo2
1Medical Digital Twin Research Group, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
Journal of translational medicine
|May 11, 2024
概括
研究人员从癌症中常见的细胞-细胞相互作用中确定了一个共享的基因特征,揭示了基因癌症相关纤维细胞 (mCAFs) 作为关键调节者. 这个签名预测了独立队列中的癌症死亡率,突出了它的预后价值.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 瘤微环境研究 研究
背景情况:
- 共享的癌症机制对于改善治疗策略和患者预后至关重要.
- 了解瘤微环境中的细胞-细胞相互作用 (CCI) 是促进癌症治疗的关键.
研究的目的:
- 在多种固体癌症中识别共享的CCI.
- 评估这些共享的CCI与癌症死亡率的关联.
主要方法:
- NicheNet分析了来自乳腺,结肠,肝脏,肺和卵巢癌的单细胞RNA测序数据,以确定CCI.
- 从已识别的CCI构建一个共享的多细胞瘤模型 (共享MCTM).
- 在癌症基因组图谱 (TCGA) 和英国生物银行 (UKBB) 队列中验证一种衍生基因签名,在mRNA和蛋白质水平上,使用Cox比例危险模型评估与10年全因死亡率的关联.
主要成果:
- 一个共享的MCTM成功衍生出来,产生了一个突出涉及矩阵癌相关纤维细胞 (mCAFs) 的基因特征.
- 该基因签名在多种癌症中显示出显著的差异表达,与独立队列中mRNA和蛋白质水平的对照相比.
- 这种特征与TCGA和UKBB队列中的癌症患者死亡率有显著的关联,对于特定癌症 (例如大脑,卵巢) 和性别观察到的风险有显著差异.
结论:
- 来自共享MCTM的新型基因特征有效地代表了不同癌症中常见的CCI.
- 这项研究强调了mCAFs在瘤微环境中的关键调节作用.
- 鉴定出的基因特征证明了癌症死亡率的致病相关性和预后价值,在大型独立队列中得到了强有力的验证.
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