Tissue biomarkers of breast cancer and their association with conventional pathologic features

Abstract

Background:Tissue protein expression profiling has the potential to detect new biomarkers to improve breast cancer (BC) diagnosis, staging, and prognostication. This study aimed to identify tissue proteins that differentiate breast cancer tissue from healthy breast tissue using protein chip mass spectrometry and to examine associations with conventional pathological features.Methods:To develop a training model, 82 BC and 82 adjacent unaffected tissue (AT) samples were analysed on cation-exchange protein chips by time-of-flight mass spectrometry. For validation, 89 independent BC and AT sample pairs were analysed.Results:From the protein peaks that were differentially expressed between BC and AT by univariate analysis, binary logistic regression yielded two peaks that together classified BC and AT with a ROC area under the curve of 0.92. Two proteins, ubiquitin and S100P (in a novel truncated form), were identified by liquid chromatography/tandem mass spectrometry and validated by immunoblotting and reactive-surface protein chip immunocapture. The combined marker panel was positively associated with high histologic grade, larger tumour size, lymphovascular invasion, ER and PR positivity, and HER2 overexpression, suggesting that it may be associated with a HER2-enriched molecular subtype of breast cancer.Conclusion:This independently validated protein panel may be valuable in the classification and prognostication of breast cancer patients.

Calcium-Binding Protein S100P Promotes Tumor Progression but Enhances Chemosensitivity in Breast Cancer

“…Other studies have since reported that activation of HER2 increases the expression of S100P in breast cancer cells ( 16 ). The relation between S100P and HER2 overexpression is only significant for ER+ tumors ( 36 ), supporting that S100P may be associated with a hormone receptor-positive, HER2 enriched molecular subtype. In the present study, the expression levels of S100P is extremely high in Luminal B HER2+ breast cancer, which is supported by previous studies ( 36 ).…”

“…The relation between S100P and HER2 overexpression is only significant for ER+ tumors ( 36 ), supporting that S100P may be associated with a hormone receptor-positive, HER2 enriched molecular subtype. In the present study, the expression levels of S100P is extremely high in Luminal B HER2+ breast cancer, which is supported by previous studies ( 36 ). This phenomenon may be more related to the “HER-enriched” breast cancer subtype ( 37 , 38 ), suggesting that S100P may have a potential for the categorization of breast cancer and to be as a therapeutic target.…”

Urinary proteome alterations in HER2 enriched breast cancer revealed by multipronged quantitative proteomics

“…Another problem with mammography is that it fails to detect the tumor in young women as dense breast tissue has a tendency to decrease mammographic sensitivity . Various quantitative proteomic‐based studies have been pursued to identify potential biomarkers for breast cancer in a variety of clinical samples such as the nipple aspirate fluids , serum , saliva , and tissue . The number of proteomics‐based studies related to breast cancer is increasing exponentially.…”

Molecular mechanism Of cell death induced by king cobra (Ophiophagus hannah) venom l-amino acid oxidase

“…Gene expression profiling is emerging as a tool for classifying breast cancers, guiding therapy, and predicting treatment outcomes (Chung et al, 2013). Breast cancer is the leading cause of cancer death in women worldwide (Jemal et al, 2011).…”