Abstract

Abstract Pancreatic cancer has a 5 year survival rate of less than 10% and this poor prognosis can be attributable to the late stage of diagnosis. Less than 20% of patients present with early stage disease, when curative surgical resection is possible. While early detection would improve outcome, presently, there is no screening method for pancreatic cancer. The current biomarker for pancreatic cancer, CA 19-9, is elevated in 70-80% of pancreatic cancer patients, but it is also elevated in about 20% of patients with benign conditions of the pancreas. There is an urgent need for the development of novel biomarkers that lead to the early diagnosis of pancreatic cancer. Biomarkers are typically developed on samples obtained at a single site and often include a substantial number of pancreatic cancer patients with advanced disease and limited numbers of diseased controls. To address these limitations, the NCI sponsored, Early Detection Research Network (EDRN) has taken the initiative to assemble a pancreatic cancer reference set (serum and plasma). The pancreatic cancer reference set contains samples from subjects with pancreatic cancer (n=100), chronic pancreatitis (n=63), acute benign biliary obstruction (n=31), and healthy controls (n=61). The characteristics of this reference set have been recently published and the marker CA19-9 assessed using this set (PLoS ONE 2015,10(10):e0139049). The features of this well characterized reference set include: collaboration and collection from multiple institutions; detailed standard operating procedure (SOP) for sample collection; pancreatic patients with resectable cancer (earlier stages); controls which included healthy and benign pancreatic and biliary conditions. The pancreatic adenocarcinomas were staged according to the criteria in the AJCC Staging Manual and the patient population consisted mainly of Stage 1 (T1N0M0 and T2N0M0) or Stage 2A (T3N0M0, absence of lymph node metastases) cancer, as confirmed by surgical pathology. The diseased controls consisted of patients with chronic pancreatitis and acute benign biliary obstruction. All blood samples were collected according to the EDRN SOP and shipped from the participating sites to the NCI Biorepository in Frederick, MD. An investigator with a promising biomarker(s) can request access to the pancreatic cancer reference set by submitting a proposal. The EDRN website has the forms for requesting access to any EDRN reference sets (http://edrn.nci.nih.gov/resources/sample-reference-sets). A number of investigators have requested and received the pancreatic reference set to test potential markers for the early detection of pancreatic cancer and publication of these results are pending. These biomarker validation studies were possible through the use of the EDRN reference set. One group of investigators showed that isoforms of apolipoprotein AII (apoAII), apoAII-ATQ/AT (C-terminal truncations of the apoAII homo-dimer) are decreased significantly in pancreatic cancer. A validation study with the EDRN pancreatic cancer reference set, along with two other independent multi-national cohorts, used a novel ELISA method for the measurement of apoAII-ATQ/AT. These isoforms were capable of distinguishing early stage of pancreatic cancer from healthy controls and also identified patient at high risk for pancreatic malignancy (Sci Rep 2015, Nov 9,5:15921). The EDRN pancreatic cancer reference set was instrumental in the validation of these candidate biomarkers. By using a common set of samples, it may be possible to create a panel of biomarkers from multiple investigators that has better performance characteristics. In conclusion, the EDRN pancreatic reference set provides a valuable resource for the validation of promising biomarkers for the early detection of pancreatic cancer. Citation Format: Jo Ann S. Rinaudo, Matthew R. Young, Randall Brand, Kazufumi Honda, Sudhir Srivastava.{Authors}. Development of a pancreatic cancer reference set for the validation of candidate biomarkers for the early detection of pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A09.

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