Walter G Park1, Liang Li2, Savitri Appana2, Wei Wei3, Kimberly Stello4, Dana K Andersen5, Steven J Hughes6, David C Whitcomb4, Randall E Brand4, Dhiraj Yadav4, Aida Habtezion7. 1. Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University, Stanford, CA, USA. Electronic address: wgpark@stanford.edu. 2. Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA. 3. Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. 4. Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. 5. Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. 6. Division of Surgical Oncology, Department of Surgery, University of Florida, Gainesville, FL, USA. 7. Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University, Stanford, CA, USA.
Abstract
OBJECTIVE: This exploratory study seeks to identify distinct circulating immune signatures among patients having recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic adenocarcinoma (PDAC). METHODS: A retrospective analysis of human serum samples from collaborating institutions of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) was performed. Samples came from the North American Pancreatitis Studies 2 (NAPS2) cohort and the Pancreatic Adenocarcinoma Gene Environment Risk Study (PAGER) and were analyzed using a 62-plex Luminex assay in a blinded fashion. Group and pairwise comparisons were performed to identify unique immune signature panels and to calculate diagnostic utility using area under the curve analysis. RESULTS: A total of 179 patients' samples were included: 41 controls, 40 CP, 78 PDAC and 20 RAP patients, of which 20 controls, 20 CP, and 58 PDAC patients had diabetes mellitus (DM). A unique immune signature panel could discriminate RAP, CP, and PDAC from controls with an AUC range from 0.77 to 0.86 (95% CI range: 0.64-0.94), RAP from CP, and CP from PDAC with an AUC of 0.77 (95% CI 0.64-0.90) and 0.76 (95% CI 0.67-0.86), respectively. Furthermore, an immune signature panel could also discriminate PDAC-DM from DM controls with an AUC of 0.96 (95% CI: 0.93-1.00) CONCLUSION: This study identifies unique immune analytes that may serve as novel diagnostic and predictive non-invasive biomarkers of RAP, CP, and PDAC. Further validation is warranted in prospective cohorts as developed by the CPDPC.
OBJECTIVE: This exploratory study seeks to identify distinct circulating immune signatures among patients having recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic adenocarcinoma (PDAC). METHODS: A retrospective analysis of human serum samples from collaborating institutions of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) was performed. Samples came from the North American Pancreatitis Studies 2 (NAPS2) cohort and the Pancreatic Adenocarcinoma Gene Environment Risk Study (PAGER) and were analyzed using a 62-plex Luminex assay in a blinded fashion. Group and pairwise comparisons were performed to identify unique immune signature panels and to calculate diagnostic utility using area under the curve analysis. RESULTS: A total of 179 patients' samples were included: 41 controls, 40 CP, 78 PDAC and 20 RAPpatients, of which 20 controls, 20 CP, and 58 PDACpatients had diabetes mellitus (DM). A unique immune signature panel could discriminate RAP, CP, and PDAC from controls with an AUC range from 0.77 to 0.86 (95% CI range: 0.64-0.94), RAP from CP, and CP from PDAC with an AUC of 0.77 (95% CI 0.64-0.90) and 0.76 (95% CI 0.67-0.86), respectively. Furthermore, an immune signature panel could also discriminate PDAC-DM from DM controls with an AUC of 0.96 (95% CI: 0.93-1.00) CONCLUSION: This study identifies unique immune analytes that may serve as novel diagnostic and predictive non-invasive biomarkers of RAP, CP, and PDAC. Further validation is warranted in prospective cohorts as developed by the CPDPC.
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