Clinical Prognostic Implications of Wnt Hub Genes Expression in Medulloblastoma

Cell Mol Neurobiol. 2023 Mar;43(2):813-826. doi: 10.1007/s10571-022-01217-4. Epub 2022 Apr 2.

Abstract

Medulloblastoma is the most common type of pediatric malignant primary brain tumor, and about one-third of patients die due to disease recurrence and most survivors suffer from long-term side effects. MB is clinically, genetically, and epigenetically heterogeneous and subdivided into at least four molecular subgroups: WNT, SHH, Group 3, and Group 4. We evaluated common differentially expressed genes between a Brazilian RNA-seq GSE181293 dataset and microarray GSE85217 dataset cohort of pediatric MB samples using bioinformatics methodology in order to identify hub genes of the molecular subgroups based on PPI network construction, survival and functional analysis. The main finding was the identification of five hub genes from the WNT subgroup that are tumor suppressors, and whose lower expression is related to a worse prognosis for MB patients. Furthermore, the common genes correlated with the five tumor suppressors participate in important pathways and processes for tumor initiation and progression, as well as development and differentiation, and some of them control cell stemness and pluripotency. These genes have not yet been studied within the context of MB, representing new important elements for investigation in the search for therapeutic targets, prognostic markers or for understanding of MB biology.

Keywords: Bioinformatics tools; Biomarkers; Hub genes; Molecular Subgroups; Therapeutic targets.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Brain Neoplasms*
  • Cerebellar Neoplasms* / genetics
  • Cerebellar Neoplasms* / metabolism
  • Cerebellar Neoplasms* / pathology
  • Child
  • Gene Expression Profiling
  • Humans
  • Medulloblastoma* / genetics
  • Medulloblastoma* / metabolism
  • Medulloblastoma* / pathology
  • Prognosis

Substances

  • Biomarkers, Tumor