Panagiota S Filippou1,2, Annie H Ren1,3, Dimitrios Korbakis1,4, Lampros Dimitrakopoulos1,3, Antoninus Soosaipillai3, Vivian Barak5, Shahar Frenkel6, Jacob Pe'er6, Michal Lotem7, Sharon Merims7, Rafael Molina8, Ivan Blasutig2, Dimitrios P Bogdanos9, Eleftherios P Diamandis1,2,3,4,10. 1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. 2. Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada. 3. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada. 4. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada. 5. Department of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 6. Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 7. Sharett Institute of Oncology, Hadassah-Hebrew University Hospital, Jerusalem, Israel. 8. Hospital Clinic, University of Barcelona, Barcelona, Spain. 9. Department of Rheumatology and Clinical Immunology, University of Thessaly, Larissa, Greece. 10. Mount Sinai Hospital, Joseph and Wolf Lebovic Ctr., 60 Murray St [Box 32], Flr 6 - Rm L6-201, Toronto, ON, M5T 3L9, Canada.
Abstract
BACKGROUND: Mucin 13 (MUC13) is a cell surface glycoprotein aberrantly expressed in a variety of epithelial carcinomas. Thus far, the role of MUC13 in various diseases remains elusive. To the best of our knowledge, this is the first study to examine the potential of MUC13 as a serum biomarker in a variety of carcinomas and other conditions. METHODS: We developed a recombinant MUC13 protein, mouse monoclonal antibodies and enzyme immunoassay (ELISA) for MUC13. We used this assay to measure MUC13 levels in the supernatants of cancer cell lines and a large cohort of serum samples from healthy and diseased individuals. RESULTS: MUC13 is secreted from cancer cell lines, with highest levels found in ovarian cancer cell lines. MUC13 levels in human sera were significantly increased in patients with renal failure and 20%-30% of patients with ovarian, liver, lung and other cancers. MUC13 was also elevated in 70% of patients with active cutaneous melanoma, but not uveal melanoma. Furthermore, we identified significant MUC13 elevations in the serum of patients with vasculitis (ANCA-positive) autoantibodies, but not in those with inflammatory bowel disease. CONCLUSIONS: Serum MUC13 is frequently elevated not only in a variety of malignant cases but also in some benign pathologies, thus appearing to be a non-specific disease biomarker. Nonetheless, serum MUC13 is clearly highly elevated in some carcinoma patients, and its relationship with tumor progression in this context warrant further research. Future studies that examine the correlation between serum MUC13 levels to stage of cancer could elucidate prognostic potential.
BACKGROUND:Mucin 13 (MUC13) is a cell surface glycoprotein aberrantly expressed in a variety of epithelial carcinomas. Thus far, the role of MUC13 in various diseases remains elusive. To the best of our knowledge, this is the first study to examine the potential of MUC13 as a serum biomarker in a variety of carcinomas and other conditions. METHODS: We developed a recombinant MUC13 protein, mouse monoclonal antibodies and enzyme immunoassay (ELISA) for MUC13. We used this assay to measure MUC13 levels in the supernatants of cancer cell lines and a large cohort of serum samples from healthy and diseased individuals. RESULTS:MUC13 is secreted from cancer cell lines, with highest levels found in ovarian cancer cell lines. MUC13 levels in human sera were significantly increased in patients with renal failure and 20%-30% of patients with ovarian, liver, lung and other cancers. MUC13 was also elevated in 70% of patients with active cutaneous melanoma, but not uveal melanoma. Furthermore, we identified significant MUC13 elevations in the serum of patients with vasculitis (ANCA-positive) autoantibodies, but not in those with inflammatory bowel disease. CONCLUSIONS: Serum MUC13 is frequently elevated not only in a variety of malignant cases but also in some benign pathologies, thus appearing to be a non-specific disease biomarker. Nonetheless, serum MUC13 is clearly highly elevated in some carcinomapatients, and its relationship with tumor progression in this context warrant further research. Future studies that examine the correlation between serum MUC13 levels to stage of cancer could elucidate prognostic potential.