First Pre-Clinical Validation Of Radiogenomics In Glioblastoma

A plethora of Magnetic Resonance Imaging (MRI) features have been correlated to cancer genomics to date, however, none have established causality. Here, we present an in vivo xenograft RNA interference validated, potentially clinically applicable test method termed “Magnetic Resonance Radiomic Sequencing” (MRRS) for the noninvasive detection of cancer genomics in Glioblastoma. MRRS comprehensively assesses the entire tumor mass using imaging texture-based algorithms that generate thousands of variables (features) inherent to the tumor. Two independent glioblastoma stem cells (GSC1 and GSC3) harboring doxycycline inducible short hairpin RNA against Periostin (POSTN), a gene previously identified in our radiogenomic screen, were implanted at orthotopic location in nude mouse brain. In vivo knockdown of u003e90% and ∼40% POSTN gene was achieved in GSC3 and GSC1 respectively. The T2 and T1 post MRI texture features, in edema and contrast enhancement phenotype features were compared between doxycycline (POSTN knockdown) and sucrose (control) group of mice using T test statistics. The significant features were included in a Stepwise Forward Logistic Regression analysis to build the final predictive model. The accuracy of the model was tested using ROC cure analysis. Among 3600 features in GSC3 mice cohort, 117 features were significantly (p value Citation Format: Pascal Zinn, Sanjay Singh, Markus M. Luedi, Faramak Zandi, Aikaterini Kotrotsou, Masumeh Hatami, Ginu Thomas, Ahmed Elakkad, Joy Gumin, Erik P. Sulman, Frederick Lang, David Piwnica-Worms, Rivka R. Colen. First pre-clinical validation of radiogenomics in glioblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4217.