Combined Proteomic-Molecular Epidemiology Approach to Identify Precision Targets in Brain Cancer

ACS Chem Neurosci. 2018 Jan 17;9(1):80-84. doi: 10.1021/acschemneuro.7b00165. Epub 2017 Jul 11.

Abstract

Primary brain tumors are predominantly malignant gliomas. Grade IV astrocytomas (glioblastomas, GBM) are among the most deadly of all tumors; most patients will succumb to their disease within 2 years of diagnosis despite standard of care. The grim outlook for brain tumor patients indicates that novel precision therapeutic targets must be identified. Our hypothesis is that the cancer proteomes of glioma tumors may contain protein variants that are linked to the aggressive pathology of the disease. To this end, we devised a novel workflow that combined variant proteomics with molecular epidemiological mining of public cancer data sets to identify 10 previously unrecognized variants linked to the risk of death in low grade glioma or GBM. We hypothesize that a subset of the protein variants may be successfully developed in the future as novel targets for malignant gliomas.

Keywords: GBM; Glioblastoma; drug target; molecular epidemiology; precision medicine; proteomic.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Data Mining
  • Drug Design*
  • Female
  • Genetic Association Studies
  • Glioma / drug therapy
  • Glioma / metabolism
  • Glioma / mortality
  • Glioma / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Molecular Epidemiology* / methods
  • Neoplasm Grading
  • Polymorphism, Single Nucleotide
  • Precision Medicine* / methods
  • Proteomics* / methods
  • Risk
  • Young Adult