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Cancer-Critical Genes II: Tumor Suppressor Genes01:05

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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
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Identification of Key Genes Associated with Overall Survival in Glioblastoma Multiforme Using TCGA RNA-Seq Expression

Lilies Handayani1,2, Denis Chegodaev1, Ray Steven1

  • 1Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 9201192, Japan.

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Deep learning models effectively identified key genes for glioblastoma multiforme (GBM) survival prediction, outperforming traditional machine learning. These findings offer novel biomarkers for this aggressive brain cancer.

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Area of Science:

  • Oncology
  • Bioinformatics
  • Genomics

Background:

  • Glioblastoma multiforme (GBM) is an aggressive brain tumor with a poor prognosis.
  • Identifying reliable molecular biomarkers is crucial for patient stratification and treatment.
  • Current treatment strategies require improved prognostic tools.

Purpose of the Study:

  • To identify key genes associated with overall survival in GBM.
  • To compare the efficacy of machine learning (ML) and deep learning (DL) approaches for GBM survival prediction.
  • To discover novel prognostic gene expression biomarkers for GBM.

Main Methods:

  • Utilized RNA-Seq gene expression and clinical data from The Cancer Genome Atlas (TCGA) for primary GBM tumors.
  • Employed univariate Cox regression to identify survival-associated genes.
  • Compared ML models (RF, GB, SVM-RFE, RF-RFE, PCA) and a DL model (DeepSurv) for survival prediction.

Main Results:

  • Univariate analysis identified 694 survival-associated genes.
  • The best ML model (RF-RFE) achieved a c-index of 0.725.
  • DeepSurv demonstrated superior predictive accuracy with a c-index of 0.822, identifying top prognostic genes like CMTR1, GMPR, and PPY.

Conclusions:

  • Deep learning, specifically DeepSurv, offers higher predictive accuracy for GBM survival compared to ML models.
  • The study identified key genes with prognostic significance, implicating purine metabolism, RNA processing, and neuroendocrine signaling pathways.
  • These findings provide valuable insights into GBM biology and highlight potential biomarkers for therapeutic development.