Met kinetic signature derived from the response to HGF/SF in a cellular model predicts breast cancer patient survival.
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.
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Gideon Y
GY
Stein
Nir
N
Yosef
Hadar
H
Reichman
Judith
J
Horev
Adi
A
Laser-Azogui
Angelique
A
Berens
James
J
Resau
Eytan
E
Ruppin
Roded
R
Sharan
Ilan
I
Tsarfaty
D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D025941:Protein Interaction Mapping / Q000379:methods; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction; D016896:Treatment Outcome
D017228:Hepatocyte Growth Factor; D011505:Protein-Tyrosine Kinases; D019859:Proto-Oncogene Proteins c-met