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Meta-Analysis of Gene Expression Signatures Defining the Epithelial to Mesenchymal Transition during Cancer Progression

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  • Christian J Gröger
  • Markus Grubinger
  • Thomas Waldhör
  • Klemens Vierlinger
  • Wolfgang Mikulits

Abstract

The epithelial to mesenchymal transition (EMT) represents a crucial event during cancer progression and dissemination. EMT is the conversion of carcinoma cells from an epithelial to a mesenchymal phenotype that associates with a higher cell motility as well as enhanced chemoresistance and cancer stemness. Notably, EMT has been increasingly recognized as an early event of metastasis. Numerous gene expression studies (GES) have been conducted to obtain transcriptome signatures and marker genes to understand the regulatory mechanisms underlying EMT. Yet, no meta-analysis considering the multitude of GES of EMT has been performed to comprehensively elaborate the core genes in this process. Here we report the meta-analysis of 18 independent and published GES of EMT which focused on different cell types and treatment modalities. Computational analysis revealed clustering of GES according to the type of treatment rather than to cell type. GES of EMT induced via transforming growth factor-β and tumor necrosis factor-α treatment yielded uniformly defined clusters while GES of models with alternative EMT induction clustered in a more complex fashion. In addition, we identified those up- and downregulated genes which were shared between the multitude of GES. This core gene list includes well known EMT markers as well as novel genes so far not described in this process. Furthermore, several genes of the EMT-core gene list significantly correlated with impaired pathological complete response in breast cancer patients. In conclusion, this meta-analysis provides a comprehensive survey of available EMT expression signatures and shows fundamental insights into the mechanisms that are governing carcinoma progression.

Suggested Citation

  • Christian J Gröger & Markus Grubinger & Thomas Waldhör & Klemens Vierlinger & Wolfgang Mikulits, 2012. "Meta-Analysis of Gene Expression Signatures Defining the Epithelial to Mesenchymal Transition during Cancer Progression," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-10, December.
    • Handle: RePEc:plo:pone00:0051136
    DOI: 10.1371/journal.pone.0051136
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    Cited by:

    1. Lining Liang & Hao Sun & Wei Zhang & Mengdan Zhang & Xiao Yang & Rui Kuang & Hui Zheng, 2016. "Meta-Analysis of EMT Datasets Reveals Different Types of EMT," PLOS ONE, Public Library of Science, vol. 11(6), pages 1-22, June.
    2. Kaori Kanemaru & Makoto Shimozawa & Manabu Kitamata & Rikuto Furuishi & Hinako Kayano & Yui Sukawa & Yuuki Chiba & Takatsugu Fukuyama & Junya Hasegawa & Hiroki Nakanishi & Takuma Kishimoto & Kazuya Ts, 2022. "Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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