%0 Journal Article
%T Met Kinetic Signature Derived from the Response to HGF/SF in a Cellular Model Predicts Breast Cancer Patient Survival
%A Gideon Y. Stein
%A Nir Yosef
%A Hadar Reichman
%A Judith Horev
%A Adi Laser-Azogui
%A Angelique Berens
%A James Resau
%A Eytan Ruppin
%A Roded Sharan
%A Ilan Tsarfaty
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0045969
%X To determine the signaling pathways leading from Met activation to metastasis and poor prognosis, we measured the kinetic gene alterations in breast cancer cell lines in response to HGF/SF. Using a network inference tool we analyzed the putative protein-protein interaction pathways leading from Met to these genes and studied their specificity to Met and prognostic potential. We identified a Met kinetic signature consisting of 131 genes. The signature correlates with Met activation and with response to anti-Met therapy (p<0.005) in in-vitro models. It also identifies breast cancer patients who are at high risk to develop an aggressive disease in six large published breast cancer patient cohorts (p<0.01, N>1000). Moreover, we have identified novel putative Met pathways, which correlate with Met activity and patient prognosis. This signature may facilitate personalized therapy by identifying patients who will respond to anti-Met therapy. Moreover, this novel approach may be applied for other tyrosine kinases and other malignancies.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0045969