Abstract 5106: Development of plasma biomarkers for pancreatic cancer diagnosis

Abstract

Abstract Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. It has the worst five year survival rate (1 to 4%) among all the cancers. This cancer is deadly because the diagnosis occurs at a late stage when the disease is inoperable and because there is a lack of effective therapy. The current pancreatic cancer biomarker CA19-9 does not provide the high sensitivity and specificity required to screen an asymptomatic population for diagnosis. Therefore, biomarkers that can improve current pancreatic cancer diagnosis would have great value to improve the patient management and survival rate of this deadly disease. In this study, we perform a large scale quantitative proteomics profiling to identify differential plasma proteins that are associated with pancreatic cancer. The proteome of plasma samples from patients with pancreatic ductal adenocarcinoma were quantitatively compared with that of non-pancreatic disease controls and patients of chronic pancreatitis, a pancreas disease that shares many molecular features with pancreatic cancer. To tackle the challenge presented by the enormous complexity and heterogeneity of plasma proteome, we applied an integrated proteomics strategy, including immunodepletion, multi-dimensional fractionations at both protein and peptide level, to enhance the detection of low abundance proteins, especially those derived from tumor cells. With stringent criteria, 1340 proteins were identified in plasma across 8-order of magnitude in protein concentration. A group of differential proteins that are associated with pancreatic cancer was identified, and their relationship with the previous studies in pancreatic tissue and pancreatic juice was investigated. A pilot study was performed to confirm a subgroup of differential proteins with ELISA using independent cohort of blood samples from well-diagnosed patients of pancreatic cancer, pancreatitis and non-pancreatic disease control. The performance of the selected protein candidates were benchmarked against CA19-9. Among the nine protein candidates tested, two demonstrated better specificity and sensitivity than CA19-9 in distinguishing pancreatic cancer from the controls; and one protein candidate was verified as a biomarker candidate for chronic pancreatitis. The protein candidates identified in this study provide a biomarker candidate pool for future development of blood-based assays for pancreatic cancer diagnosis. The discovery and technical strategy presented by this study may be pertinent to biomarker development for other cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5106. doi:10.1158/1538-7445.AM2011-5106