Abstract
Background: Epithelial-mesenchymal transition (EMT) is regulated by induction factors, transcription factor families and an array of signaling pathways genes, and has been implicated in the invasion and progression of gliomas.Methods: We obtained the Clinicopathological data sets from Chinese Glioma Genome Atlas (CGGA). The “limma” package was used to analyze the expression of EMT-related genes in gliomas with different pathological characteristics. We used the “ConsensusClusterPlus” package to divide gliomas into two groups to study their correlation with glioma malignancy. The least absolute shrinkage and selection operator (LASSO) Cox regression was applied to select seven prognosis-associated genes to build the risk signature, and the coefficients obtained from the LASSO algorithm were used to calculate the risk score which we applied to determine the prognostic value of the risk signature. Univariate and multivariate Cox regression analyses were used to determine whether the risk signature is an independent prognostic indicator.Results: We analyzed the differentially expressed 22 common epithelial-mesenchymal transition-associated genes in 508 gliomas graded by different clinicopathological features. Two glioma subgroups (EM1/2) were identified by consistent clustering of the proteins, of which the EM1 subgroup had a better prognosis than the EM2 subgroup, and the EM2 group was associated with cancer migration and proliferation. Significant enrichment analysis revealed that EMT-related transcriptional regulators and signaling pathways genes were highly related to glioma malignancies. Seven EMT-related genes were used to derive risk scores, which served as independent prognostic markers and prediction factors for the clinicopathological features of glioma. And we found the overall survival (OS) was significantly different between the low- and high-risk groups, the ROC curve indicated that the risk score can predict survival rates for glioma patients.Conclusion: EMT-related induction factors, transcriptional regulators and signaling pathways genes are important players in the malignant progression of glioma and may help in decision making regarding the choice of prognosis assessment and provide us clues to understand EMT epigenetic modification in glioma.
Highlights
Glioblastoma (GBM) is the most malignant and most aggressive tumor of the brain [1]
Because Epithelial-mesenchymal transition (EMT) is determined to be closely related to glioma malignancies, we systematically studied the relationship between variables and the pathological characteristics of glioma, including WHO grade, IDH status, and 1p/19q codeletion status
The heatmap reveals that the expression of most EMT induction factors, transcription factors, and signaling pathways genes is significantly correlated with the WHO level
Summary
Glioblastoma (GBM) is the most malignant and most aggressive tumor of the brain [1]. The basal membrane of these cells exhibits a variety of cellular processes that makes them manifest different mesenchymal cell phenotypes, including invasiveness and migration, anti-apoptosis and high levels of ECM [4]. It is essential in wound healing, stem cell characteristics and in tissue fibrosis which determines cancer deterioration [5]. This indicates that EMT contributes to the invasiveness of glioblastoma. Epithelial-mesenchymal transition (EMT) is regulated by induction factors, transcription factor families and an array of signaling pathways genes, and has been implicated in the invasion and progression of gliomas
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