Urokinase plasminogen activator receptor, plasminogen activator inhibitor- 1,extracellular matrix metalloproteinase protein inducer and CA 15-3 as potential biomarkers for diagnosis and prognosis of primary breast cancer

Abstract

Breast cancer is one of the most important leading causes of cancer deathin the less developed countries.The identification of markers that could assist in diagnosis, evaluation of therapeutic response, detection of recurrence and metastasis is a useful tool. The present study is undertaken to provide insights about the role of urokinase plasminogen activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), extracellular matrix metalloproteinase protein inducer (EMMPRIN), cancer antigen (CA) 15-3 in diagnosis and/or prognosis of breast cancer, evaluate the possible correlations between these biomarkers and the clinico-pathological status of breast cancer and compare between validity of these biomarkers with tumor marker (CA 15-3). A total of 75 women whose ages ranged between 30 to70 years and 10 healthy controls with matched age and sex were included. The patients were divided into 4 groups, group I: Included 39 female patients with breast cancer before operation, group II: Included 17 women from group I followed for 6 months after operation, group III: Included 9 women from group I followed for 12 months after operation, group IV: Included 10 female patients with benign breast diseases. Estimation of serum uPAR, PAI-1, EMMPRIN and CA 15-3 by ELISA and related clinico-pathological features were assessed. The results revealed higher mean serum levels of uPAR, PAI-1, EMMPRIN and CA 15-3 in breast cancer women before operation when compared to other 4 groups. Patients after 6 and 12 months follow up showed a decrement of uPAR, EMMPRIN, PAI-1 and CA 15-3 levels.There was significant relationbetween uPAR, PAI-1, EMMPRIN, CA 15-3 and clinicopathological characteristic of breast cancer patients. There was a significant positive correlation between serum uPAR, PAI-1 and EMMPRIN (p<0.001).In conclusion, High circulating uPAR, PAI-1 andEMMPRIN were significantly associated with breast carcinogenesis and metastasis. Accordingly, estimation of these biomarkers may predict the breast disease behavior and its prognosis.

Key words:Breast cancer,CA 15-3,EMMPRIN, PAI-1, uPAR