Proteomic analysis of tissue samples in translational breast cancer research

Abstract

In the last decade, many proteomic technologies have been applied, with varying success, to the study of tissue samples of breast carcinoma for protein expression profiling in order to discover protein biomarkers/signatures suitable for: characterization and subtyping of tumors; early diagnosis, and both prognosis and prediction of outcome of chemotherapy. The purpose of this review is to critically appraise what has been achieved to date using proteomic technologies and to bring forward novel strategies – based on the analysis of clinically relevant samples – that promise to accelerate the translation of basic discoveries into the daily breast cancer clinical practice. In particular, we address major issues in experimental design by reviewing the strengths and weaknesses of current proteomic strategies in the context of the analysis of human breast tissue specimens.

Keywords::

• breast cancer
• gel-based proteomics
• immunohistochemistry
• peptide-centric proteomics
• protein arrays
• tumor heterogeneity

Financial & competing interests disclosure

This work was supported by the Danish Cancer Society through the budget of the Research Center and by grants from the “Race against Breast Cancer” foundation and the John and Birthe Meyer Foundation. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Much progress has been achieved in proteomics discovery technologies allowing in-depth profiling of proteome in a multiple breast tissue cancer samples that are a promise in improving the understanding of breast cancer progression and in establishment of novel tissue-based prognostic, diagnostic and predictive biomarkers and/or signatures.

• However, finding protein biomarkers which can be implemented in daily clinical practice has turned out to be not a simple task. Many steps and elements of the translational proteomic strategies used to date in translational breast cancer studies should be critically reviewed to achieve a better success in future.

• Considerations with regard to intratumor heterogeneity and plasticity should be carefully taken into account in any breast cancer proteomic projects.

• So far, the most of the translational proteomic studies were generally executed on a limited number of tissue samples with an insufficient knowledge about breast cancer patients.

• Validation tests are usually performed on small cohort of samples that are often poorly characterized. Stratification of the data obtained at the discovery phase is a crucial step in creating clinically relevant reliable biomarkers.

Notes