System-wide Clinical Proteomics of Breast Cancer Reveals Global Remodeling of Tissue Homeostasis

Abstract

The genomic and transcriptomic landscapes of breast cancer have been extensively studied, but the proteomes of breast tumors are far less characterized. Here, we use high-resolution, high-accuracy mass spectrometry to perform a deep analysis of luminal-type breast cancer progression using clinical breast samples from primary tumors, matched lymph node metastases, and healthy breast epithelia. We used a super-SILAC mix to quantify over 10,000 proteins with high accuracy, enabling us to identify key proteins and pathways associated with tumorigenesis and metastatic spread. We found high expression levels of proteins associated with protein synthesis and degradation in cancer tissues, accompanied by metabolic alterations that may facilitate energy production in cancer cells within their natural environment. In addition, we found proteomic differences between breast cancer stages and minor differences between primary tumors and their matched lymph node metastases. These results highlight the potential of proteomic technology in the elucidation of clinically relevant cancer signatures.

Selecting Sample Preparation Workflows for Mass Spectrometry-Based Proteomic and Phosphoproteomic Analysis of Patient Samples with Acute Myeloid Leukemia

“…Lately, 2DE has been used to analyze saliva from individuals with and without oral leukoplakia [37]. However, as found in our study on AML patient samples, the FASP procedure and the use of a super-SILAC mix of five cell lines [38] have proved to be excellent methodologies for quantitative proteomics of breast cancer samples [39]. …”

Perseus: A Bioinformatics Platform for Integrative Analysis of Proteomics Data in Cancer Research

“…In the subsequent analysis, we used a subset of the data measured by Pozniak et al [20]. The authors provide a genome-wide proteomic analysis of progression of breast cancer in patients by studying major differences at the proteome level between healthy, primary tumor, and metastatic tissues.…”

Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer

“…To identify tumor-associated signatures, onco-proteomics studies have investigated cell lines, mice xenografts, or entire biopsies (Geiger et al., 2012, Guo et al., 2015, Ntai et al., 2016, Pozniak et al., 2016, Zhang et al., 2016). However, cell lines recapitulate biology of neoplastic cells within an actual tumor only to a certain extent, and other cell types may contaminate mouse xenografts or entire tissues.…”