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A Tyrosine Kinase Expression Signature Predicts the Post-Operative Clinical Outcome in Triple Negative Breast Cancers

1
Department of Medical Oncology, Institut Paoli-Calmettes, Aix-Marseille Univ, CRCM, CNRS, INSERM, 13000 Marseille, France
2
Laboratory of Predictive Oncology, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Inserm UMR1068, CNRS UMR725, Aix-Marseille Université, 13000 Marseille, France
3
Department of Surgical Oncology, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, CRCM, 13000 Marseille, France
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1158; https://doi.org/10.3390/cancers11081158
Received: 15 July 2019 / Revised: 4 August 2019 / Accepted: 9 August 2019 / Published: 13 August 2019
(This article belongs to the Special Issue New Insights into Breast and Endometrial Cancer)
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Abstract

Triple negative breast cancer (TNBC) represent 15% of breast cancers. Histoclinical features and marketed prognostic gene expression signatures (GES) failed to identify good- and poor-prognosis patients. Tyrosine kinases (TK) represent potential prognostic and/or therapeutic targets for TNBC. We sought to define a prognostic TK GES in a large series of TNBC. mRNA expression and histoclinical data of 6379 early BCs were collected from 16 datasets. We searched for a TK-based GES associated with disease-free survival (DFS) and tested its robustness in an independent validation set. A total of 1226 samples were TNBC. In the learning set of samples (N = 825), we identified a 13-TK GES associated with DFS. This GES was associated with cell proliferation and immune response. In multivariate analysis, it outperformed the previously published GESs and classical prognostic factors in the validation set (N = 401), in which the patients classified as “low-risk” had a 73% 5-year DFS versus 53% for “high-risk” patients (p = 1.85 × 10−3). The generation of 100,000 random 13-gene signatures by a resampling scheme showed the non-random nature of our classifier, which was also prognostic for overall survival in multivariate analysis. We identified a robust and non-random 13-TK GES that separated TNBC into subgroups of different prognosis. Clinical and functional validations are warranted. View Full-Text
Keywords: triple negative breast cancer; tyrosine kinase; gene expression signature; prognosis triple negative breast cancer; tyrosine kinase; gene expression signature; prognosis
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de Nonneville, A.; Finetti, P.; Adelaide, J.; Lambaudie, É.; Viens, P.; Gonçalves, A.; Birnbaum, D.; Mamessier, E.; Bertucci, F. A Tyrosine Kinase Expression Signature Predicts the Post-Operative Clinical Outcome in Triple Negative Breast Cancers. Cancers 2019, 11, 1158.

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