Chakraborty Priyanka, Chen Emily L, McMullen Isabelle, Armstrong Andrew J, Kumar Jolly Mohit, Somarelli Jason A
Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India.
Department of Medicine, Durham, NC, United Kingdom.
Comput Struct Biotechnol J. 2021 Jun 17;19:3842-3851. doi: 10.1016/j.csbj.2021.06.023. eCollection 2021.
Epithelial-mesenchymal plasticity plays a critical role in many solid tumor types as a mediator of metastatic dissemination and treatment resistance. In addition, there is also a growing appreciation that the epithelial/mesenchymal status of a tumor plays a role in immune evasion and immune suppression. A deeper understanding of the immunological features of different tumor types has been facilitated by the availability of large gene expression datasets and the development of methods to deconvolute bulk RNA-Seq data. These resources have generated powerful new ways of characterizing tumors, including classification of immune subtypes based on differential expression of immunological genes. In the present work, we combine scoring algorithms to quantify epithelial-mesenchymal plasticity with immune subtype analysis to understand the relationship between epithelial plasticity and immune subtype across cancers. We find heterogeneity of epithelial-mesenchymal transition (EMT) status both within and between cancer types, with greater heterogeneity in the expression of EMT-related factors than of MET-related factors. We also find that specific immune subtypes have associated EMT scores and differential expression of immune checkpoint markers.
上皮-间质可塑性在许多实体瘤类型中作为转移扩散和治疗抗性的介质发挥着关键作用。此外,人们也越来越认识到肿瘤的上皮/间质状态在免疫逃逸和免疫抑制中起作用。大型基因表达数据集的可用性以及对批量RNA测序数据进行反卷积分析方法的发展,促进了对不同肿瘤类型免疫特征的更深入理解。这些资源产生了强大的新方法来表征肿瘤,包括基于免疫基因差异表达对免疫亚型进行分类。在本研究中,我们将用于量化上皮-间质可塑性的评分算法与免疫亚型分析相结合,以了解癌症中上皮可塑性与免疫亚型之间的关系。我们发现癌症类型内部和之间上皮-间质转化(EMT)状态存在异质性,EMT相关因子的表达比MET相关因子的表达具有更大的异质性。我们还发现特定的免疫亚型具有相关的EMT评分和免疫检查点标志物的差异表达。