Abstract 2719: Non-invasive biomarker discovery for ovarian cancer

Abstract

Abstract The majority of women with ovarian cancer are diagnosed with advanced disease (FIGO stage III and IV) and have a five year survival rate of approximately 20%. In contrast, the survival rate of women diagnosed with stage I ovarian cancer is greater than 90%, highlighting an unmet and dire need for accurate and reliable diagnostic tests for the early detection of ovarian cancer. We have previously demonstrated that urinary matrix metalloproteinases (MMPs) are independent predictors of disease status and stage in a variety of human cancers as well as predictors of breast cancer risk. We have also reported that neutrophil gelatinase-associated lipocalin (NGAL) is present in the urine of women with metastatic breast cancer and that the levels of urinary NGAL are significantly higher in these patients compared to normal controls. In the current study, we asked whether urinary MMPs and NGAL, alone or in combination, could provide useful clinical information with respect to the presence of ovarian cancer. Urine samples were obtained from a total of 166 women: 96 women with known FIGO stage III and IV ovarian cancer (newly diagnosed and recurrent) and 70 normal controls. All urine samples were analyzed for NGAL levels by ELISA and for urinary MMP levels by quantitative gelatin zymography. We found that urinary NGAL, MMP9-dimer, MMP9/NGAL complex, MMP9, and MMP2 were each significantly elevated in the urine of women with ovarian cancer compared to normal controls (p<0.001). Receiver operating characteristic (ROC) curve analysis indicated that the area under the curve (AUC) for each individual urinary matrix metalloproteinase biomarker and NGAL was statically significant: AUC= 0.706 for MMP9-dimer (p<0.001), AUC=0.645 for MMP9/NGAL complex (p<0.001), AUC= 0.712 for MMP9 (p<0.001), AUC=0.681 for MMP2 (p<0.001), and AUC=0.668 for NGAL (p<0.001). Among these biomarkers, multivariable logistic regression confirmed that MMP9-dimer multiplexed with MMP2 (MMP9-dimer/MMP2) provided optimal diagnostic information for differentiating between the ovarian cancer and control groups AUC = 0.753, (95% confidence interval (CI) = 0.680 – 0.827, (p<0.001)). Interestingly, when these multivariate predictors were combined with another known risk factor for ovarian cancer, that being age, we found that women >55 years of age with significant measurable levels of urinary MMP9-dimer and MMP2 had a 95% probability of ovarian cancer (95% CI= 85-98% probability), AUC = 0.860 (95% CI = 0.802 – 0.915 (p<0.001)). Taken together, these data suggest that the panel of urinary biomarkers composed of gelatinases, their complexes and NGAL, along with patient age, may provide clinically useful information with respect to distinguishing between women who have ovarian cancer and those who do not. (Supported by NIH P01 CA045548, the Weitzman Family Foundation and Ovations for the Cure) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2719.