Radiogenomic analysis of hypoxia pathway is predictive of overall survival in Glioblastoma

Sci Rep. 2018 Jan 8;8(1):7. doi: 10.1038/s41598-017-18310-0.

Abstract

Hypoxia, a characteristic trait of Glioblastoma (GBM), is known to cause resistance to chemo-radiation treatment and is linked with poor survival. There is hence an urgent need to non-invasively characterize tumor hypoxia to improve GBM management. We hypothesized that (a) radiomic texture descriptors can capture tumor heterogeneity manifested as a result of molecular variations in tumor hypoxia, on routine treatment naïve MRI, and (b) these imaging based texture surrogate markers of hypoxia can discriminate GBM patients as short-term (STS), mid-term (MTS), and long-term survivors (LTS). 115 studies (33 STS, 41 MTS, 41 LTS) with gadolinium-enhanced T1-weighted MRI (Gd-T1w) and T2-weighted (T2w) and FLAIR MRI protocols and the corresponding RNA sequences were obtained. After expert segmentation of necrotic, enhancing, and edematous/nonenhancing tumor regions for every study, 30 radiomic texture descriptors were extracted from every region across every MRI protocol. Using the expression profile of 21 hypoxia-associated genes, a hypoxia enrichment score (HES) was obtained for the training cohort of 85 cases. Mutual information score was used to identify a subset of radiomic features that were most informative of HES within 3-fold cross-validation to categorize studies as STS, MTS, and LTS. When validated on an additional cohort of 30 studies (11 STS, 9 MTS, 10 LTS), our results revealed that the most discriminative features of HES were also able to distinguish STS from LTS (p = 0.003).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / mortality
  • Female
  • Gene Expression Profiling
  • Genomics / methods
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism*
  • Glioblastoma / mortality
  • Humans
  • Hypoxia / genetics*
  • Hypoxia / metabolism*
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Signal Transduction

Substances

  • Biomarkers