Abstract 4798: Pilot study of plasma biomarker candidates for pancreatic cancer detection - a targeted proteomics approach

Abstract

Abstract With the advances in genomics and proteomics, the number of biomarker candidates associated with pancreatic cancer has increased explosively in recent years. Many putative biomarkers have been discovered in pancreatic tumor tissue and pancreatic juice; such targets will need to be rigorously verified in plasma or serum for blood-based biomarker development. Currently, validation of putative biomarkers in blood largely relies on antibody creation for ELISA assays, and has been the bottleneck for biomarker development. Analytical techniques to robustly measure these proteins in plasma, which is arguably the most complex biological matrix with protein abundance exceeding 10 orders of magnitude, has been a challenge. In this study, we applied a mass spectrometry-based targeted proteomics platform to directly detect candidate biomarker proteins in plasma to evaluate their clinical utility for pancreatic cancer diagnosis. The characterization of these protein candidates used a clinically well-characterized cohort that included plasma samples from patients with pancreatic cancer, chronic pancreatitis and healthy age-matched controls. Based on the receiver operating characteristic (ROC) analysis, two of the five candidate proteins tested, demonstrated an Area Under Curve (AUC) value greater than 0.89 in the detection of pancreatic cancer from healthy controls and chronic pancreatitis controls. We further demonstrated that a composite biomarker by combining two complementary independent biomarkers improves the sensitivity for pancreatic cancer detection at 95% specificity. Based on this evidence, these biomarker candidates merit further validation in larger patient and control cohorts for their potential utility in clinical application. In addition, we provide an analysis of the reproducibility, accuracy, and robustness of the mass spectrometry-based targeted proteomics platform. This information addresses important technical issues that could aid in the adoption of the targeted proteomics platform for practical clinical utility. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4798. doi:1538-7445.AM2012-4798