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Molecular signaling network complexity is correlated with cancer patient survivability
Dylan Breitkreutz, Lynn Hlatky, Edward Rietman and Jack A. Tuszynski
Proceedings of the National Academy of Sciences of the United States of America
Vol. 109, No. 23 (June 5, 2012), pp. 9209-9212
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/41603076
Page Count: 4
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The 5-y survival for cancer patients after diagnosis and treatment is strongly dependent on tumor type. Prostate cancer patients have a > 99% chance of survival past 5 y after diagnosis, and pancreatic patients have < 6% chance of survival past 5 y. Because each cancer type has its own molecular signaling network, we asked if there are "signatures" embedded in these networks that inform us as to the 5-y survival. In other words, are there statistical metrics of the network that correlate with survival? Furthermore, if there are, can such signatures provide clues to selecting new therapeutic targets? From the Kyoto Encyclopedia of Genes and Genomes Cancer Pathway database we computed several conventional and some less conventional network statistics. In particular we found a correlation (R² = 0.7) between degree-entropy and 5-y survival based on the Surveillance Epidemiology and End Results database. This correlation suggests that cancers that have a more complex molecular pathway are more refractory than those with less complex molecular pathway. We also found potential new molecular targets for drugs by computing the betweenness—a statistical metric of the centrality of a node—for the molecular networks.
Proceedings of the National Academy of Sciences of the United States of America © 2012 National Academy of Sciences