Targeted proteomics driven verification of biomarker candidates associated with breast cancer aggressiveness
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
28216224
DOI
10.1016/j.bbapap.2017.02.012
PII: S1570-9639(17)30036-5
Knihovny.cz E-resources
- Keywords
- Breast cancer, Estrogen receptor, Lymph node, Selected reaction monitoring, Tumor grade, mTRAQ,
- MeSH
- Adult MeSH
- Actin Depolymerizing Factors biosynthesis genetics MeSH
- Neoplasm Invasiveness genetics pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphatic Metastasis MeSH
- Lymph Nodes metabolism pathology MeSH
- Cell Adhesion Molecules biosynthesis genetics MeSH
- Biomarkers, Tumor biosynthesis genetics MeSH
- Neoplasm Proteins biosynthesis genetics MeSH
- Breast Neoplasms genetics pathology MeSH
- Disease-Free Survival MeSH
- Prognosis MeSH
- RNA-Binding Proteins biosynthesis genetics MeSH
- Proteomics MeSH
- Receptors, Estrogen genetics MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Aged MeSH
- Stathmin biosynthesis genetics MeSH
- Thrombospondins biosynthesis genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Actin Depolymerizing Factors MeSH
- Cell Adhesion Molecules MeSH
- Biomarkers, Tumor MeSH
- Neoplasm Proteins MeSH
- POSTN protein, human MeSH Browser
- RNA-Binding Proteins MeSH
- Receptors, Estrogen MeSH
- SERBP1 protein, human MeSH Browser
- Stathmin MeSH
- STMN1 protein, human MeSH Browser
- thrombospondin 2 MeSH Browser
- Thrombospondins MeSH
Breast cancer is the most common and molecularly relatively well characterized malignant disease in women, however, its progression to metastatic cancer remains lethal for 78% of patients 5years after diagnosis. Novel markers could identify the high risk patients and their verification using quantitative methods is essential to overcome genetic, inter-tumor and intra-tumor variability and translate novel findings into cancer diagnosis and treatment. We recently identified 13 proteins associated with estrogen receptor, tumor grade and lymph node status, the key factors of breast cancer aggressiveness, using untargeted proteomics. Here we verified these findings in the same set of 96 tumors using targeted proteomics based on selected reaction monitoring with mTRAQ labeling (mTRAQ-SRM), transcriptomics and immunohistochemistry and validated in 5 independent sets of 715 patients using transcriptomics. We confirmed: (i) positive association of anterior gradient protein 2 homolog (AGR2) and periostin (POSTN) and negative association of annexin A1 (ANXA1) with estrogen receptor status; (ii) positive association of stathmin (STMN1), cofilin-1 (COF1), plasminogen activator inhibitor 1 RNA-binding protein (PAIRBP1) and negative associations of thrombospondin-2 (TSP2) and POSTN levels with tumor grade; and (iii) positive association of POSTN, alpha-actinin-4 (ACTN4) and STMN1 with lymph node status. This study highlights a panel of gene products that can contribute to breast cancer aggressiveness and metastasis, the understanding of which is important for development of more precise breast cancer treatment.
References provided by Crossref.org
Breast Cancer Classification Based on Proteotypes Obtained by SWATH Mass Spectrometry
