BioMedBC pipeline included the integration of existing and newly acquired high resolution -omics datasets by machine learning algorithms and systems biology approaches.
Within WP1, the prognostic potential of urinary biomarkers based on Capillary Electrophoresis coupled to Mass Spectrometry (CE-MS) was investigated. 36 peptides were identified with a significant correlation with BC relapse (hazard ratio (HR) of 5.76 (CI 95%, 2.35-14.12) p-value = 0.0001). Among the significant urinary peptides were collagen alpha-1 fragments, fibrinogen, polymeric immunoglobulin receptor, nebulin, forkhead box protein D2 and CD99 antigen.
As part of WP2, tissue proteomics datasets were acquired from 45 BC patients (during MSCA-IF Fellow's secondment). Combination with existing high throughput proteomics and transcriptomics data was followed to perform pathway analysis and identify molecular pathways associated to disease outcome. 444 genes and 500 proteins were found consistently deregulated across BC stages in the omics datasets. 293 common features were identified and were considered for pathway analysis. 46 significant pathways were obtained using Reactome. 20 of the identified pathways, including Interferon, Interleukin-12, FGFR1 and P53 signalling, were previously investigated in BC and 17 others were related to cancer in general.
Within WP3, validation of the prognostic value of the previous results was performed. CE-MS analysis was performed in 710 newly acquired urine samples, confirming the positive corelation of the biomarkers with BC relapse (HR of 2.57; 1.10-6.02; 95% CI). Further validation was performed considering the tissue proteomics datasets (WP2) and publicly available gene expression data from TCGA. Additional analysis using CMap based on the high-resolution proteomics data revealed 14 drugs, predicted to reverse the BC phenotype, that are to be further explored for their clinical significance.
Exploitation and Dissemination
BioMedBC also focused on dissemination and training activities (WP4). Dissemination, among others, was achieved through publication of 6 articles in scientific journals, participation in international meetings, an oral presentation in a MSCA fellow meeting, launch of BioMedBC website and an interview for H2020 magazin. Moreover, the MSCA- IF fellow edited a Special Issue in Proteomics Clinical Applications Journal, highlighting the value of clinical implementation of proteomics in the era of personalised medicine. Training included mentoring and ethical courses, and active interaction with H2020 MSCA-ITN Fellows and INNOSUP research Associates.
The exploitation of BioMedBC results was achieved as part of the translation of existing scientific knowledge into potentially clinically meaningful biomarkers. In the context of the clinical trials in the field of BC, we have communicated the BioMedBC biomarkers, as stratification/companion tools to pharmaceutical industry. Relevant flyers were also produced to inform BC patients on the prognostic markers and their clinical potiential.
