Abstract 5567: Pancreatic disease-specific carriers of the CA 19-9 antigen identified by antibody microarrays and mass spectrometry

Abstract

Abstract Distinguishing patients with malignant pancreatic tumors from those with benign conditions is critical for doctors to make proper treatment decisions. However, this process is usually costly and invasive due to the lack of a simple detection method such as a blood test. The current standard serological biomarker of pancreatic cancer, the CA 19-9 antigen, is not accurate enough for early diagnosis due to its occasional elevation in benign pancreatic diseases. The CA 19-9 antigen is a carbohydrate epitope found on multiple protein carriers. We sought to determine whether the protein carriers of the CA 19-9 antigen are different between benign and malignant pancreatic disease, and whether these differences could be harnessed to develop improved biomarkers. Two approaches were used to investigate this question. In the first, we used antibody microarrays to capture multiple different mucins from the sera of early-stage pancreatic cancer patients (n = 33), late-stage pancreatic cancer patients (n = 17), pancreatitis patients (n = 38), and healthy control subjects (n = 20), and we probed the level of the CA 19-9 antigen on the captured proteins using a monoclonal antibody. Pancreatic cancer progression was associated with a shift in CA 19-9 carriers from MUC16 to MUC1 and MUC5AC. Certain monoclonal antibodies captured glycoforms of MUC1 that predominantly carried CA 19-9 in the cancer patients. Because of that relationship, the detection of CA 19-9 on specific protein glycoforms improved the discrimination of cancer from control subjects over total CA 19-9 (AUC= 0.93 vs. AUC=0.86. In the second approach, we immunoprecipitated CA19-9 carrier proteins from pooled sera of late-stage cancer, early-stage cancer, pancreatitis, and control subjects, followed by deglycosylation and mass spectrometry (MALDI/TOF/TOF). Several proteins were identified in the sera of the cancer patients but not in the sera of pancreatitis or control subjects, indicating the possible identification of state-specific carriers of CA 19-9. Ongoing studies are aimed at verifying these identifications and testing performance as biomarkers of pancreatic cancer. These findings may lead to more accurate methods of discriminating benign from malignant pancreatic disease, which would improve the ability to render proper care to patients at the earliest possible stages. 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 5567.