Met Kinetic Signature Derived from the Response to HGF/SF in a Cellular Model Predicts Breast Cancer Patient Survival |
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Authors: | Gideon Y. Stein Nir Yosef Hadar Reichman Judith Horev Adi Laser-Azogui Angelique Berens James Resau Eytan Ruppin Roded Sharan Ilan Tsarfaty |
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Affiliation: | 1. Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.; 2. Department of Internal Medicine “B”, Beilinson Hospital, Rabin Medical Center, Petah-Tikva, Israel.; 3. Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.; 4. Van Andel Research Institute, Grand Rapids, Michigan, United States of America.; University of Nebraska Medical Center, United States of America, |
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Abstract: | 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. |
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