Abstract 5105: Towards a multiparametric biomarker panel for pancreatic cancer detection

Abstract

Abstract Pancreatic cancer is one of the most highly lethal of all solid malignancies for which serological biomarkers to aid in the detection and clinical management of patients are urgently needed. To date, the lack of a single highly specific and sensitive marker for pancreatic cancer detection has led to a growing consensus in the field towards the development of panels of biomarkers, where-by the combinatorial assessment of multiple biomarkers will likely result in increased sensitivity and specificity. In this respect, we previously characterized the conditioned media of six pancreatic cancer cell lines (MIA-PaCa2, BxPc3, PANC1, Su.86.86, CAPAN1, CFPAC1) and the normal human pancreatic ductal epithelial cell line HPDE, as well as six pancreatic juice samples from pancreatic ductal adenocarcinoma patients using strong cation exchange followed by reverse-phase coupled online to an LTQ-Orbitrap mass spectrometer. This resulted in the identification of 3810 non-redundant proteins in the cell lines and 648 proteins in the pancreatic juice. All proteins were identified with 2 or more peptides. Through subsequent bioinformatic analyses which included hierarchical clustering, label-free protein quantification between the cancer and normal cell lines, cellular localization, tissue specificity and integration of the proteomes from the multiple biological fluids, a list of candidate pancreatic cancer biomarkers was generated. Preliminary verification of selected candidates using enzyme-linked immunosorbent assays (ELISAs) in a screening set of plasma samples from pancreatic cancer patients and healthy age-sex matched controls (n=40) show five proteins (designated PANC1, PANC2, PANC3, PANC4 and PANC5) to be significantly increased in pancreatic cancer plasma (p=0.0011, p<0.0001, p<0.0001, p<0.0001 and p=0.0098, respectively). Individually, these proteins did not exhibit improved area under the curve (AUC) in comparison to CA19.9 levels measured in the same samples; however the combination of the five proteins with CA19.9 showed improved AUC to CA19.9 alone (CA19.9 alone AUC = 0.97; all proteins with CA19.9 AUC = 1.0). These data suggest that this novel panel warrants further evaluation as a pancreatic cancer diagnostic tool. 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 5105. doi:10.1158/1538-7445.AM2011-5105