Transcriptomic-Based Quantification of the Epithelial-Hybrid-Mesenchymal Spectrum across Biological Contexts.

Transcriptomic-Based Quantification of the Epithelial-Hybrid-Mesenchymal Spectrum across Biological Contexts.
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DOI:
10.3390/biom12010029
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发表时间:
2021-12-25
期刊:
影响因子:
5.5
通讯作者:
Jolly MK
Jolly MK
中科院分区:
生物学2区
文献类型:
--
作者:
Mandal S;Tejaswi T;Janivara R;Srikrishnan S;Thakur P;Sahoo S;Chakraborty P;Sohal SS;Levine H;George JT;Jolly MK

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上皮-间质可塑性(EMP)是胚胎发育、伤口愈合、癌症转移和纤维化的基础。表现出EMP的癌细胞通常具有更具侵略性的行为,其特征在于耐药性以及肿瘤引发和免疫逃避特性。因此,癌细胞的EMP状态可以是患者预后的关键指标。在这里,我们比较了三种不同的基于转录组学的指标-每个指标都使用不同的基因列表和算法来量化EMP谱。我们对80多个癌症相关RNA测序数据集的结果显示,这些指标在量化EMP程度方面具有高度一致性。此外,尽管每个指标都是在癌症表达谱上训练的,但都概括了非癌症背景下EMP评分的预期变化,如肺纤维化和细胞重编程为诱导多能干细胞。因此,我们提供了一个评分平台来量化EMP在体外和体内的程度,用于包括癌症在内的各种生物学应用。
Epithelial-mesenchymal plasticity (EMP) underlies embryonic development, wound healing, and cancer metastasis and fibrosis. Cancer cells exhibiting EMP often have more aggressive behavior, characterized by drug resistance, and tumor-initiating and immuno-evasive traits. Thus, the EMP status of cancer cells can be a critical indicator of patient prognosis. Here, we compare three distinct transcriptomic-based metrics—each derived using a different gene list and algorithm—that quantify the EMP spectrum. Our results for over 80 cancer-related RNA-seq datasets reveal a high degree of concordance among these metrics in quantifying the extent of EMP. Moreover, each metric, despite being trained on cancer expression profiles, recapitulates the expected changes in EMP scores for non-cancer contexts such as lung fibrosis and cellular reprogramming into induced pluripotent stem cells. Thus, we offer a scoring platform to quantify the extent of EMP in vitro and in vivo for diverse biological applications including cancer.
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