Abstract
Blood-based early detection of breast cancer has recently gained novel momentum, as liquid biopsy diagnostics is a fast emerging field. In this study, we aimed to identify secreted proteins which are up-regulated both in tumour tissue and serum samples of breast cancer patients compared to normal tissue and sera. Based on two independent tissue cohorts (n = 75 and n = 229) and one serum cohort (n = 80) of human breast cancer and healthy serum samples, we characterised AGR3 as a novel potential biomarker both for breast cancer prognosis and early breast cancer detection from blood. AGR3 expression in breast tumours is significantly associated with oestrogen receptor α (P<0.001) and lower tumour grade (P<0.01). Interestingly, AGR3 protein expression correlates with unfavourable outcome in low (G1) and intermediate (G2) grade breast tumours (multivariate hazard ratio: 2.186, 95% CI: 1.008-4.740, P<0.05) indicating an independent prognostic impact. In sera analysed by ELISA technique, AGR3 protein concentration was significantly (P<0.001) elevated in samples from breast cancer patients (n = 40, mainly low stage tumours) compared to healthy controls (n = 40). To develop a suitable biomarker panel for early breast cancer detection, we measured AGR2 protein in human serum samples in parallel. The combined AGR3/AGR2 biomarker panel achieved a sensitivity of 64.5% and a specificity of 89.5% as shown by receiver operating characteristic (ROC) curve statistics. Thus our data clearly show the potential usability of AGR3 and AGR2 as biomarkers for blood-based early detection of human breast cancer.
Highlights
Breast cancer remains the most frequently diagnosed and leading cause of cancer deaths in women worldwide [1]
AGR3 mRNA expression is increased in G1/G2 grade and luminal breast tumours compared to normal tissue controls
The current study is the first to analyse in depth the AGR3 expression, as well as its potential clinical relevance in breast cancer
Summary
Breast cancer remains the most frequently diagnosed and leading cause of cancer deaths in women worldwide [1]. Therewith, early detection remains a major challenge in the management of breast cancer. Mammography has become the standard of care for breast cancer screening [3] several limitations are known concerning this procedure, such as a poor accuracy in women with dense breast parenchyma resulting in reduced clinical sensitivity and specificity [3,4]. For women at high risk to develop breast cancer, supplemental magnetic resonance imaging (MRI), an expensive technique that offers excellent imaging even around dense breast tissue, is applied [3]. The high sensitivity of MRI (85% to 100%) is compromised by a high rate of false positives (37% to 100%) resulting in unnecessary follow-up examinations (including invasive biopsies) causing further stress for the patient and costs [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
