CXCL12 and CXCR4 as Potential Early Biomarkers for Luminal A and Luminal B Subtypes of Breast Cancer

Abstract

Joanna Motyka,1 Ewa Gacuta,2 Aleksandra Kicman,3 Monika Kulesza,1 Paweł Malinowski,4 Sławomir Ławicki1 1Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok, Bialystok, Poland; 2Department of Perinatology, University Clinical Hospital of Bialystok, Bialystok, Poland; 3Department of Aesthetic Medicine, Medical University of Bialystok, Bialystok, Poland; 4Department of Oncological Surgery, Bialystok Oncology Center, Bialystok, PolandCorrespondence: Joanna Motyka, Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok, Jerzego Waszyngtona 15B str, Bialystok, 15-269, Poland, Tel [phone], Email [email protected]: Breast cancer is the most common type of malignancy in women. Factors that increase the risk of occurrence include chronic inflammation, with chemokines as its mediators. Therefore, the purpose of the present study was to determine the diagnostic utility of CXCL12 and CXCR4 as modern tumor markers in patients with early-stage luminal A and luminal B subtype of breast cancer and also to compare the results with the routinely used marker – CA 15-3.Patients and Methods: The study included 100 patients with early breast cancer of luminal A and B subtypes, 50 women with benign breast lesion and 50 healthy women. The levels of CXCL12 and CXCR4 concentrations were determined by enzyme-linked immunosorbent assay (ELISA), comparative marker CA 15-3 – by electrochemiluminescence method (ECLIA).Results: Concentrations of CXCL12 were significantly lower, while CXCR4 and CA 15-3 – significantly higher among patients with early-stage breast cancer than healthy women. CXCL12 also showed lower concentrations among fibroadenoma patients in comparison to healthy women, while CXCR4 – lower concentrations among fibroadenoma patients than cancer group. CXCL12 showed significantly higher values of sensitivity (79%), specificity (82%), positive predictive value (89.72%), negative predictive value (80%), diagnostic accuracy (80%) and diagnostic power (AUC = 0.8196) in the whole breast cancer group compared to the CA 15-3 marker (58%; 72%; 80.56%; 46.15%, 62.67%, 0.6434, resp.). Analysis of combined parameters resulted in increased sensitivity, negative predictive value and power of the test with a slight decrease in positive predictive value and a more significant decrease in specificity, reaching the best values for the three-parameter test CXCL12+CXCR4+CA15-3 (96%; 85.71%; AUC = 0.8812; 78.69%; 48%, resp.).Conclusion: The results indicate the preliminary usefulness of CXCL12 and CXCR4 as early biomarkers in the diagnosis of breast cancer, especially in the combined panel with CA 15-3.Keywords: breast cancer, luminal, CXCL12, CXCR4, biomarkers, early diagnosis

Keywords

• breast cancer
• luminal
• cxcl12
• cxcr4
• biomarkers
• early diagnosis;