Cells (Mar 2021)

A New Epigenetic Model to Stratify Glioma Patients According to Their Immunosuppressive State

  • Maurizio Polano,
  • Emanuele Fabbiani,
  • Eva Andreuzzi,
  • Federica Di Cintio,
  • Luca Bedon,
  • Davide Gentilini,
  • Maurizio Mongiat,
  • Tamara Ius,
  • Mauro Arcicasa,
  • Miran Skrap,
  • Michele Dal Bo,
  • Giuseppe Toffoli

DOI
https://doi.org/10.3390/cells10030576
Journal volume & issue
Vol. 10, no. 3
p. 576

Abstract

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Gliomas are the most common primary neoplasm of the central nervous system. A promising frontier in the definition of glioma prognosis and treatment is represented by epigenetics. Furthermore, in this study, we developed a machine learning classification model based on epigenetic data (CpG probes) to separate patients according to their state of immunosuppression. We considered 573 cases of low-grade glioma (LGG) and glioblastoma (GBM) from The Cancer Genome Atlas (TCGA). First, from gene expression data, we derived a novel binary indicator to flag patients with a favorable immune state. Then, based on previous studies, we selected the genes related to the immune state of tumor microenvironment. After, we improved the selection with a data-driven procedure, based on Boruta. Finally, we tuned, trained, and evaluated both random forest and neural network classifiers on the resulting dataset. We found that a multi-layer perceptron network fed by the 338 probes selected by applying both expert choice and Boruta results in the best performance, achieving an out-of-sample accuracy of 82.8%, a Matthews correlation coefficient of 0.657, and an area under the ROC curve of 0.9. Based on the proposed model, we provided a method to stratify glioma patients according to their epigenomic state.

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