title: AGR3 in breast cancer: prognostic impact and suitable serum-based biomarker for early cancer detection.
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.
authors: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors: Stefan
authors: S
authors: Garczyk
authors: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors: Saskia
authors: S
authors: von Stillfried
authors: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors: Wiebke
authors: W
authors: Antonopoulos
authors: Institute of Pathology, University Hospital Erlangen, Erlangen, Germany.
authors: Arndt
authors: A
authors: Hartmann
authors: Department of Gynaecology and Obstetrics, University Hospital Erlangen, Erlangen, Germany.
authors: Michael G
authors: MG
authors: Schrauder
authors: Department of Gynaecology and Obstetrics, University Hospital Erlangen, Erlangen, Germany.
authors: Peter A
authors: PA
authors: Fasching
authors: Patients' Tumor Bank of Hope (PATH) Foundation, München, Germany.
authors: Tobias
authors: T
authors: Anzeneder
authors: Institute of Pathology, Ruhr-University Bochum, Bochum, Germany, on behalf of the PATH Biobank group.
authors: Andrea
authors: A
authors: Tannapfel
authors: Department for Senology, St Anna Hospital, Herne, Germany, on behalf of the PATH Biobank group.
authors: Yavuz
authors: Y
authors: Ergönenc
authors: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors: Ruth
authors: R
authors: Knüchel
authors: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors: Michael
authors: M
authors: Rose
authors: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors: Edgar
authors: E
authors: Dahl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009088:Mucoproteins; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins; D011379:Prognosis; D016016:Proportional Hazards Models; D011506:Proteins / Q000378:metabolism; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C502296:AGR2 protein, human; C472588:AGR3 protein, human; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D009088:Mucoproteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D011506:Proteins