Pancreatic cancer is the fifth leading cause of cancer death in the USA. This is due, in part, to the lack of early detection methods for this particularly aggressive form of cancer. None of the biomarkers of pancreatic cancer that have been identified to date are sufficiently predictive to be useful as a diagnostic or screening test. We hypothesize that a multi-marker panel will have high sensitivity and specificity for early detection of pancreatic cancer. We propose to use novel Luminex LabMAP technology that allows for simultaneous evaluation of multiple (up to 100) biomarkers in one sample. Our preliminary results suggest that our Luminex panel has significant predictive power. Our goal is to develop a reliable serum-based assay for early detection of pancreatic cancer based on the longitudinal patterns of multiple biomarkers. This project is firmly based on biomarker discoveries and strong preliminary data developed and include a team of basic cancer researchers and clinicians supported by faculty with requisite expertise in biostatistics/bioinformatics. Our immediate objectives are (i) to further expand our pancreatic cancer panel with additional pancreatic cancer-relevant biomarkers including circulating antibodies and (ii) to interpret the panel longitudinally and validate the resultant assay for patient use. To accomplish these objectives the following Specific Aims are proposed: 1. Generate and optimize a comprehensive multiplexed assay for detection of highly relevant pancreatic cancer markers. Luminex-based assay will be developed for multiplex analysis of most of the known pancreatic cancer serological biomarkers including cytokines, chemokines, angiogenic and growth factors and their receptors, as well as circulating antibodies against pancreatic antigens. 2. Use Luminex-based biomarker panels identified to select a combined multimarker panel that distinguishes patients with pancreatic cancer from healthy controls or patients with benign disease (Phase 2 validation study). Performance characteristics of biomarker panels developed in Aim I will be evaluated in a definitive cohort with adenocarcinoma of the pancreas, chronic pancreatitis, acute pancreatitis, and patients with other peri-ampullary tumors and age-, sex- and smoking status-matched healthy controls. A combination of markers allowing distinguishing patients with pancreatic cancer from those without cancer or with benign disease will be selected. The cancer-specificity of this panel will be assessed. An optimized statistical model for analyzing and combining multimarker panels will be developed. 3. Validate/optimize this multimarker panel in retrospective longitudinal study (Phases 3-4 validation study). Diagnostic utility of the multimarker assay in a general population will be validated in available prospective studies. At the conclusion of this study, we expect to develop strategies for the early detection of pancreatic cancer that are practical and efficient and can be projected to offer the best opportunity to reduce the mortality from this disease. This research study will be conducted in the context of UPCI EDRN/BDL directed by Dr. Anna Lokshin, who brings extensive experience in cancer biomarkers and Luminex multiplexed technology research. The combined team comprises an outstanding and productive group of clinical and translational cancer researchers focused on cancer biomarkers discovery, evaluation, and validation. These efforts will strongly support the research and clinical goals of the EDRN. ? ?
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