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.
Highlights
HER2/neu receptors and account for about 15% of all breast cancers
Several proteomic studies have been conducted on triple-negative breast cancers (TNBC) [3,4,5], but no proteomic study was conducted on large cohorts including the clinical outcome of the patients, except a recent comparative proteome analysis that identified a 11-protein signature for aggressive TNBC in a large cohort of 93 microdissected tumors [6]
In this context, taking into account the tumor microenvironment, we investigated a cohort of 83 TNBC samples without microdissection by a quantitative proteomic approach using iTRAQ labeling
Summary
HER2/neu receptors and account for about 15% of all breast cancers This subtype is associated with poor prognosis [1] in terms of distant free survival (DFS) and overall survival (OS), and to date, there is no clinically available targeted therapy for patients diagnosed with TNBC. We established a protein signature of the most aggressive tumors. Follow-up data were collected for all patients, including, disease-free survival (DFS; time from diagnosis to first recurrence of the disease or contralateral breast cancer or second primary other cancer) and overall survival (OS, time from diagnosis to death from any cause).
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