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

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 therapynaive 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. Molecular & Cellular

Advancement of mass spectrometry-based proteomics technologies to explore triple negative breast cancer

“…Overexpression of DP and TPS1 significantly altered the disease free survival and enhanced the risk of recurrence of TNBC patients. However, it was also reported that overexpression of TrpRS was associated with better disease free patient survival and lower risk of recurrence 98 . Another iTRAQ labelling based proteomics study identified several factors which have strong associations with molecular subtypes of breast cancer (fibronectin, alpha-2-macroglobulin (A2M), complement component-4-binding protein alpha (C4BPA) and complement factor-B).…”

“…Both iTRAQ and TMT strategies have been broadly employed in cancer studies for drug discovery 49 , investigating cancer signaling 50 , as well as for investigating diagnostic and prognosis markers 51 . iTRAQ has also been employed to predict cancer recurrence and patient survival in triple negative breast tissue samples 52 . Although these approaches have shown merit, they are less accurate and sensitive compared with SILAC, as the tag is added at a later stage of the procedure, resulting in lower proteome coverage 53 .…”

“…This study also elucidated TNBC-specific signalling pathways involved in metastasis, adhesion and angiogenesis 13 . Different expression signatures for three proteins desmoplain (DP), thrombospondin-1 (TPS1) and trytophanyl-tRNA synthase (TrpRS) were discovered for relapse and non-relapse TBNC tumours using an iTRAQ labelling based proteomic approach 98 . Overexpression of DP in luminal breast cells 99 and the metastatic and proangiogenic activity of TPS1 100 in breast cancer cells had been previously reported.…”

iTRAQ‐Based Quantitative Proteomic Analysis Strengthens Transcriptomic Subtyping of Triple‐Negative Breast Cancer Tumors

“…Transcriptome screening was performed using Affymetrix Human Genome U133 Plus 2.0 Arrays (Affymetrix, Santa Clara, CA) measuring over 54 000 transcripts representing over 20 000 human genes. These two methods have been fully described in previous works …”

Human expression patterns: qualitative and quantitative analysis of thrombospondin‐1 under physiological and pathological conditions

“…In accordance to its anti‐angiogenic property, high tumour expression of TSP‐1 is correlated with increased patient survival in colon, lung, bladder, ovarian, cervical and gastric cancer . However, high tumour tissue TSP‐1 is also associated with decreased survival in patients with hepatocellular carcinoma, breast cancer and melanoma . Along with the observation that high VEGF in cancer is usually associated with worse prognosis and increased metastasis, it is very likely that certain types of cancer (eg breast cancer) may have developed compensatory mechanisms to counteract the anti‐angiogenic pathways activated by TSP‐1 .…”