title: Surprisal analysis of Glioblastoma Multiform (GBM) microRNA dynamics unveils tumor specific phenotype.
abstract: Gliomablastoma multiform (GBM) is the most fatal form of all brain cancers in humans. Currently there are limited diagnostic tools for GBM detection. Here, we applied surprisal analysis, a theory grounded in thermodynamics, to unveil how biomolecule energetics, specifically a redistribution of free energy amongst microRNAs (miRNAs), results in a system deviating from a non-cancer state to the GBM cancer -specific phenotypic state. Utilizing global miRNA microarray expression data of normal and GBM patients tumors, surprisal analysis characterizes a miRNA system response capable of distinguishing GBM samples from normal tissue biopsy samples. We indicate that the miRNAs contributing to this system behavior is a disease phenotypic state specific to GBM and is therefore a unique GBM-specific thermodynamic signature. MiRNAs implicated in the regulation of stochastic signaling processes crucial in the hallmarks of human cancer, dominate this GBM-cancer phenotypic state. With this theory, we were able to distinguish with high fidelity GBM patients solely by monitoring the dynamics of miRNAs present in patients' biopsy samples. We anticipate that the GBM-specific thermodynamic signature will provide a critical translational tool in better characterizing cancer types and in the development of future therapeutics for GBM.
authors.affiliation: Institute of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Sohila
authors.initials: S
authors.lastname: Zadran
authors.affiliation: Department of Chemistry, B6c, University of Liege, Liege, Belgium.
authors.forename: Francoise
authors.initials: F
authors.lastname: Remacle
authors.affiliation: Crump Institute for Molecular Imaging and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Raphael
authors.initials: R
authors.lastname: Levine
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D013269:Stochastic Processes; D013816:Thermodynamics
chemical_list: D035683:MicroRNAs