Abstract
Abstract Pancreatic malignancies are 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. A majority of patients with pancreatic malignancies, including both pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (pNET) present with advanced disease due to a lack of specific symptoms and current diagnostic limitations, making this disease extremely difficult to detect. The 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 discovery 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. In the current study, our goal was to determine whether ADAM12 (a disintegrin and metalloprotease 12) could be detected in the urine of patients with pancreatic malignancies and whether ADAM12 levels might serve as an independent predictor of disease status. Retrospective analyses of urine samples (n=130) from PDAC and pNET patients as well as age- and sex-matched controls were conducted. Urinary ADAM12 levels were determined using a monospecific ELISA system. In addition, ADAM12 protein expression in tumor and normal pancreatic tissues was analyzed via immunohistochemistry (IHC). Multivariable logistic regression analyses indicated that, when controlling for age and sex, urinary ADAM12 could serve as significant independent predictor for distinguishing PDAC (P<0.001) and pNET (P<0.008) patients from healthy controls. Kaplan-Meier analysis of estimated patient survival stratified by urinary ADAM12 levels indicated a significantly shorter patient survival time for PDAC patients with high ADAM12 levels (P=0.015) compared to patients with lower urinary ADAM12. In addition, IHC analysis indicated that ADAM12 protein expression was upregulated ∼4-fold in Grade I-III PDAC compared to normal pancreatic tissue. Taken together, our results suggest that the measurement of ADAM12 levels may have diagnostic value in detection and/or clinical monitoring of disease status in patients with pancreatic malignancies. [Supported by: The Advanced Medical Foundation] Citation Format: Roopali Roy, David Zurakowski, Matthew Kulke, Marsha A. Moses. Urinary ADAM12 levels detect the presence of pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 891. doi:10.1158/1538-7445.AM2014-891
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