Rivka Rachel Colen MD, Presenter: Nothing to Disclose

Prateesh Sathyan, Abstract Co-Author: Nothing to Disclose

Ashok J. Kumar MD, Abstract Co-Author: Nothing to Disclose

Pascal O. Zinn MD, Abstract Co-Author: Nothing to Disclose

The search for an effective therapy of Glioblastoma Multiforme (GBM) continues. Imaging Genomics, a newly emerged field, links gene expression profiles with MRI phenotypes (Zinn et al, 2011). MRI-FLAIR was found to correlate with cellular invasion in GBM; thus, whole genome quantitative imaging analysis can reveal functional microRNA-gene regulatory networks as novel targets for cellular invasion in GBM. We sought to validate MRI as a screening tool for genomic target discovery.

We performed radiogenomic mapping of MRI- and corresponding genomic data in 78 TCGA patients. The top microRNA-gene regulatory network was biologically validated by functional and mechanistic in-invitro and invivo orthotopic xenograft model studies using gain and loss of function. Small animal 7T MRI-T2/FLAIR was used for imaging-genomic validations.

The top up-regulated gene in high invasion MRI phenotypes was PERIOSTIN (POSTN). The top down-regulated microRNA (miR-219) was validated to bind to POSTN.  MRI-T2/FLAIR signal highly correlated with POSTN levels and the degree of cellular invasion in orthotopic xenograft models. Furthermore, high POSTN and a high POSTN/miR-219 signature resulted in decreased survival and shorter time to progression (P<0.0001) in 511 GBM patients.

In this study, we validated a novel noninvasive diagnostic method to screen for functional networks of cellular invasion. POSTN inhibition can be a novel therapeutic approach to target invasion in GBM. Furthermore, targeted individualized molecular therapies can be based on diagnostic imaging-genomics and can be monitored through-out the treatment period.

Imaging, specifically MRI, can be used as a screening method in order to identify genomic targets that are clinically meaningful and can potentially go on to develop genomic based therapeutics.

Colen, R, Sathyan, P, Kumar, A, Zinn, P, Validating MRI as a Screening Tool for Genomic Target Discovery for Therapeutic Drug Development.  Radiological Society of North America 2013 Scientific Assembly and Annual Meeting, December 1 - December 6, 2013 ,Chicago IL. http://archive.rsna.org/2013/13016665.html