Abstract
Breast cancers are the most common cancer-affecting women; critically the identification of novel biomarkers for improving early detection, stratification and differentiation from benign tumours is important for the reduction of morbidity and mortality.To identify and functionally characterise potential biomarkers, we used mass spectrometry (MS) to analyse serum samples representing control, benign breast disease (BBD) and invasive breast cancer (IDC) patients. Complementary and multidimensional proteomic approaches were used to identify and validate novel serum markers.Annexin A3 (ANX A3) was found to be differentially expressed amongst different breast pathologies. The diagnostic value of serum ANX A3 was subsequently validated by ELISA in an independent serum set representing the three groups. Here, ANX A3 was significantly upregulated in the benign disease group sera compared with other groups (P < 0.0005).In addition, paired breast tissue immunostaining confirmed that ANX A3 was abundantly expressed in benign and to a lesser extent malignant neoplastic epithelium. Finally, we illustrated ANX A3 expression in cell culture lysates and conditioned media from neoplastic breast cell lines, and its role in neoplastic breast cell migration in vitro.This study confirms the novel role of ANX A3 as a mammary biomarker, regulator and therapeutic target.
Highlights
Breast cancer is the most common malignancy and the second leading cause of cancer related death in women [1,2,3]
The intensity of this ion was observed to be stronger in the benign disease compared to the invasive ductal carcinoma (IDC) group, significant differential expression was not detected between either the IDC versus benign breast disease (BBD) (P = 0.43), or the IDC versus control groups (P = 0.90)
In this study we mined for potential novel breast cancer serum biomarkers
Summary
Breast cancer is the most common malignancy and the second leading cause of cancer related death in women [1,2,3]. Diagnosis and more effective treatment regimens have led to a paradoxical improvement of survival rates despite an increasing breast cancer incidence over the last few decades [5,6,7]. Screening programs lead to an estimated 15% reduction in breast cancer mortality, they were subsequently shown to be associated with 30% risk of www.impactjournals.com/oncotarget over-diagnosis and treatment [9,10,11]. Prediction and stratification of breast disease at an early stage would further improve patients’ outcome and quality of life. Markers that reduce the incidence of “missed” or delayed breast cancer diagnosis would reduce the rate of excessive surgical and percutaneous benign biopsies improving diagnostic pathways, screening programs and patients’ well-being. Existing biochemical markers are of limited value in assessing and stratifying breast cancer risk in the healthy population [12,13,14,15]
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