Pan-cancer Network Disorders Revealed by Overall and Local Signaling Entropy.

Tumor development is a process involving loss of the differentiation phenotype and acquisition of stem-like characteristics, which is driven by intracellular rewiring of signaling network. The measurement of network reprogramming and disorder would be challenging due to the complexity and heterogeneity of tumors. Here, we proposed signaling entropy to assess the degree of tumor network disorder. We calculated signaling entropy for 33 tumor types in The Cancer Genome Atlas database based on transcriptomic and proteomic data. The signaling entropy of tumors was significantly higher than that of normal samples and was highly correlated with cell stemness, cancer type, tumor grade, and metastasis. We further demonstrated the sensitivity and accuracy of using local signaling entropy in prognosis prediction and drug response evaluation. Overall, signaling entropy could reveal cancer network disorders related to tumor malignant potency, clinical prognosis, and drug response.