On dynamic network entropy in cancer

TL;DR

This study shows that cancer cells exhibit increased dynamic network entropy, which correlates with their robustness and ability to adapt, providing insights into potential therapeutic targets by analyzing gene expression and network dynamics.

Contribution

The paper introduces a novel approach linking gene expression, network entropy, and cancer cell robustness, demonstrating systemic differences between normal and cancer states.

Findings

Cancer cells have higher dynamic network entropy than normal cells.

Genes involved in proliferation show decreased local entropy in cancer.

Higher entropy correlates with increased robustness to perturbations.

Abstract

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.