Prediction of Recurrence and Survival for Triple-Negative Breast Cancer (TNBC) by a Protein Signature in Tissue Samples

Mario Campone; Isabelle Valo; Pascal Jézéquel; Marie Moreau; Alice Boissard; Loic Campion; Delphine Loussouarn; Véronique Verriele; Olivier Coqueret; Catherine Guette

doi:10.1074/mcp.M115.048967

Prediction of Recurrence and Survival for Triple-Negative Breast Cancer (TNBC) by a Protein Signature in Tissue Samples

Mol Cell Proteomics. 2015 Nov;14(11):2936-46. doi: 10.1074/mcp.M115.048967. Epub 2015 Jul 24.

Authors

Affiliations

¹ ‡René Gauducheau ICO Cancer Center, Inserm U892, CNRS 6299, Bd J. Monod, 44805 Saint Herblain Cedex, France; §Paul Papin ICO Cancer Center, Inserm U892, CNRS 6299, 2 rue Moll, 49933 Angers Cedex 9, France;
² §Paul Papin ICO Cancer Center, Inserm U892, CNRS 6299, 2 rue Moll, 49933 Angers Cedex 9, France;
³ ‡René Gauducheau ICO Cancer Center, Inserm U892, CNRS 6299, Bd J. Monod, 44805 Saint Herblain Cedex, France;
⁴ ¶Angers University, 4 Boulevard de Lavoisier, Angers, 49000, France;
⁵ ‖INSERM U892, CNRS 6299, IRT-UN, 8 quai Moncousu, 44007 Nantes Cedex, France.
⁶ §Paul Papin ICO Cancer Center, Inserm U892, CNRS 6299, 2 rue Moll, 49933 Angers Cedex 9, France; ¶Angers University, 4 Boulevard de Lavoisier, Angers, 49000, France;
⁷ §Paul Papin ICO Cancer Center, Inserm U892, CNRS 6299, 2 rue Moll, 49933 Angers Cedex 9, France; catherine.guette@ico.unicancer.fr.

Abstract

To date, there is no available targeted therapy for patients who are diagnosed with triple-negative breast cancers (TNBC). The aim of this study was to identify a new specific target for specific treatments. Frozen primary tumors were collected from 83 adjuvant therapy-naive TNBC patients. These samples were used for global proteome profiling by iTRAQ-OFFGEL-LC-MS/MS approach in two series: a training cohort (n = 42) and a test set (n = 41). Patients who remains free of local or distant metastasis for a minimum of 5 years after surgery were classified in the no-relapse group; the others were in the relapse group. OPLS and Kaplan-Meier analyses were performed to select candidate markers, which were validated by immunohistochemistry. Three proteins were identified in the training set and validated in the test set by Kaplan-Meier method and immunohistochemistry (IHC): TrpRS as a good prognostic markers and DP and TSP1 as bad prognostic markers. We propose the establishment of an IHC test to calculate the score of TrpRS, DP, and TSP1 in TNBC tumors to evaluate the degree of aggressiveness of the tumors. Finally, we propose that DP and TSP1 could provide therapeutic targets for specific treatments.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Biomarkers, Tumor / genetics*
Biomarkers, Tumor / metabolism
Desmoplakins / genetics
Desmoplakins / metabolism
Female
Gene Expression Regulation, Neoplastic*
Humans
Immunohistochemistry
Isocitrate Dehydrogenase / genetics
Isocitrate Dehydrogenase / metabolism
Middle Aged
Neoplasm Grading
Neoplasm Recurrence, Local / diagnosis*
Neoplasm Recurrence, Local / genetics
Neoplasm Recurrence, Local / mortality
Neoplasm Recurrence, Local / pathology
Prognosis
ROC Curve
Receptor, ErbB-2 / deficiency
Receptor, ErbB-2 / genetics
Receptors, Estrogen / deficiency
Receptors, Estrogen / genetics
Receptors, Progesterone / deficiency
Receptors, Progesterone / genetics
Survival Analysis
Tandem Mass Spectrometry
Thrombospondin 1 / genetics
Thrombospondin 1 / metabolism
Triple Negative Breast Neoplasms / diagnosis*
Triple Negative Breast Neoplasms / genetics
Triple Negative Breast Neoplasms / mortality
Triple Negative Breast Neoplasms / pathology
Tryptophan-tRNA Ligase / genetics*
Tryptophan-tRNA Ligase / metabolism

Substances

Biomarkers, Tumor
Desmoplakins
Receptors, Estrogen
Receptors, Progesterone
Thrombospondin 1
IDH2 protein, human
Isocitrate Dehydrogenase
ERBB2 protein, human
Receptor, ErbB-2
Tryptophan-tRNA Ligase