Pancreatic cancer is the fourth leading cause of all cancer-related deaths of both men and women in the United States. Each year, approximately 32,000 new patients are diagnosed with this disease and nearly the same number die from it. This disease is extremely difficult to diagnose in its early stages due to a lack of specific symptoms and the limitations of current diagnostic methods. A combination of poor prognosis and late presentation of pancreatic cancer patients highlights the urgent need for the development of effective, early detection strategies for this disease. Our laboratory has established a comprehensive biomarker identification initiative whose objective is to identify proteins present in urine of cancer patients, to determine whether their presence might be relevant to disease status and stage and to validate their diagnostic and prognostic efficacy in large scale clinical trials. We have reported that matrix metalloproteases (MMPs) can be detected in the urine of patients with a variety of cancers including prostate, bladder, renal, and breast and are independent predictors of disease status and stage in cancer patients. The objective of the current study was to determine whether urinary MMP species and/or their endogenous inhibitors, tissue inhibitors of metalloproteases (TIMPs) could be detected in the urine of pancreatic cancer patients and if so, whether they might serve as independent predictors of disease status. Retrospective analyses of urine samples (n=135) from pancreatic adenocarcinoma, and neuroendocrine cancer patients as well as age- and sex-matched controls were conducted using a combination of gelatin zymography, ELISA and immunoblot methods. Four MMP and one TIMP species were reproducibly detected in the urine of pancreatic cancer patients: MMP-2, MMP-9, MMP-9/NGAL complex, MMP-9 dimer and TIMP-1. Multivariate logistic regression analysis indicated that, when controlling for age and sex, MMP-2 (p<0.0001) and TIMP-1 (p<0.0001) were significant independent predictors for distinguishing pancreatic adenocarcinoma patients from healthy controls. These data also indicate that MMP-2 (p<0.0001) was an independent predictor of the presence of neuroendocrine cancer. In addition, the presence of urinary MMP-9 dimer (p=0.02) and TIMP-1 (p<0.001) could differentiate neuroendocrine cancers from adenocarcinomas within the disease groups. Our results suggest that the detection of a panel of urinary MMPs and TIMP-1 may be of diagnostic value in the detection and/or clinical monitoring of disease status in patients with pancreatic cancer. [Supported by: NIH PO1 CA45548, The Jo Ann Webb Fund for Angiogenesis Research and The Advanced Medical Foundation]

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1583.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009