Role of serum-derived hyaluronan-associated protein-hyaluronan complex in ovarian cancer

The objective of this study was to determine if the level of serum hyaluronan (HA), serum-derived HA-associated protein (SHAP)-HA complex, and urinary trypsin inhibitor (UTI) correlate with the clinical outcome of ovarian cancer patients. The relationship of metalloproteinase and its inhibitor with HA and the SHAP-HA complex was also examined. Serum and urine samples were obtained from 45 patients with ovarian cancer, 22 patients with benign ovarian tumors and 50 healthy women. Concentrations of serum HA and UTI were measured by an inhibitory sandwich enzyme-linked immunosorbent assay, and concentrations of the serum SHAP-HA complex were measured by a sandwich enzyme-linked immunosorbent assay. Concentrations of MMP-2, MMP-9 and TIMP-1 were measured by a one-step enzyme immunoassay. The levels of HA, SHAP-HA complex, MMP-9 and TIMP-1 were higher in the ovarian cancer group than in the benign ovarian tumor group. In ovarian cancer patients, the levels of HA, SHAP-HA complex and MMP-9 were higher in the stage III/IV group than in the stage I/II group, and the levels of SHAP-HA complex, MMP-9 and TIMP-1 were higher in the non-responder group than in the responder group. The serum concentration of SHAP-HA complex had a significant correlation with HA, MMP-9 and TIMP-1 in ovarian cancer patients. The patients with elevated SHAP-HA complex had a shorter disease-free survival compared with those with normal levels of SHAP-HA complex. The multiple regression analysis revealed that SHAP-HA complex is the significant independent variable for progression-free survival. The elevated level of SHAP-HA complex may indicate the prognosis of recurrence and reflect the tumor metastasis associated with MMP-9 in ovarian cancer patients.