Gibbs Free Energy of Protein-Protein Interactions Reflects Tumor Stage

 Gibbs Free Energy of Protein-Protein Interactions reflects tumor stage 

Edward A. Rietman1 , Alex Bloemendal2 , John Platig3 , Jack A. Tuszynski4,5, Giannoula Lakka Klement1,6*

1. Molecular Oncology Research Institute, Tufts Medical Center, Boston, 02111 2. Mathematics Department, Harvard University, Cambridge, MA 3. Dana-Farber Cancer Institute, Boston, MA 4. Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 1Z2 5. Department of Physics, University of Alberta, Edmonton, Alberta, Canada T6G 2E1 6. Pediatric Hematology Oncology, Floating Hospital for Children at Tufts Medical Center, Boston, MA 

Abstract The sequential changes occurring with cancer progression are now being harnessed with therapeutic intent. Yet, there is no understanding of the chemical thermodynamics of proteomic changes associated with cancer progression/ cancer stage. This manuscript reveals a strong correlation of a chemical thermodynamic measure (known as Gibbs free energy) of protein-protein interaction networks for several cancer types and 5-year overall survival and stage in patients with cancer. Earlier studies have linked degree entropy of signaling networks to patient survival data, but not with stage. It appears that Gibbs free energy is a more general metric and accounts better for the underlying energetic landscape of protein expression in cells, thus correlating with stage as well as survival.

This is an especially timely finding because of improved ability to obtain and analyze genomic/ proteomic information from individual patients. Yet, at least at present, only candidate gene imaging (FISH or immunohistochemistry) can be used for entropy computations. With continually expanding use of genomic information in clinical medicine, there is an ever-increasing need to understand the thermodynamics of protein-protein interaction networks.