An individualized transcriptional signature to predict the epithelial-mesenchymal transition based on relative expression ordering

The epithelial-mesenchymal transition (EMT) process is involved in cancer cell metastasis and immune system activation. Hence, identification of gene expression signatures capable of predicting the EMT status of cancer cells is essential for development of therapeutic strategies. However, quantitative identification of EMT markers is limited by batch effects, the platform used, or normalization methods. We hypothesized that a set of EMT-related relative expression orderings are highly stable in epithelial samples yet are reversed in mesenchymal samples. To test this hypothesis, we analyzed transcriptome data for ovarian cancer cohorts from publicly available databases, to develop a qualitative 16-gene pair signature (16-GPS) that effectively distinguishes the mesenchymal from epithelial phenotype. Our method was superior to previous quantitative methods in terms of classification accuracy and applicability to individualized patients without requiring data normalization. Patients with mesenchymal-like ovarian cancer showed poorer overall survival compared to patients with epithelial-like ovarian cancer. Additionally, EMT score was positively correlated with expression of immune checkpoint genes and metastasis. We, therefore, established a robust EMT 16-GPS that is independent of detection platform, batch effects and individual variations, and which represents a qualitative signature for investigating the EMT and providing insights into immunotherapy for ovarian cancer patients.