Henrik Johansson (Solna / SE), Akram Emdadi (Solna / SE), Mahshid Zarrineh (Solna / SE), Ioannis Siavelis (Solna / SE), Haris Babacic (Solna / SE), Eduardo Araujo (Solna / SE), Rui Branca (Solna / SE), Johan Staaf (Lund / SE), Janne Lehtiö (Solna / SE)
Henrik J. Johansson1, Akram Emdadi1, Mahshid Zarrineh1, Ioannis Siavelis1, Haris Babacic1, Eduardo Araujo1, Rui M. Branca1, Johan Staaf2, Janne Lehtiö1.
1Department of Oncology and Pathology, Karolinska Institutet, SciLifeLab, Solna, Sweden
2Division of Oncology, Department of Clinical Sciences, Lund and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden
Triple negative breast cancer (TNBC) has the worst prognosis in breast cancer with limited therapy options. Here we investigate the phenotypic proteome level of TNBC using mass spectrometry (MS) based proteomics methods, with the aim to foster a better biological understanding of TNBC, identify subtypes and link them to therapy response for proteome precision medicine.
The multi-omics population-based discovery cohort consists of 225 TNBC samples from SCANB in Sweden with WGS, RNA-seq, data independent acquisition (DIA) and TMT based quantitative MS based proteomics data. The TMT based proteomics data is generated using peptide fractionation using immobilized pH gradient-isoelectric focusing (IPG-IEF) before nanoLC-MS/MS, which enable searching a 6-reading frame translation of the human genome to identify novel protein coding regions and potential neoantigens.
In the discovery cohort we have identified subtypes with different biological characteristics and clinical outcomes. For validation of the subtypes and linking them to drug response we are developing proteome-based classifiers based on the DIA data and are acquiring DIA data from clinical trials with chemo- and immunotherapy.