Michele T Yip-Schneider1,2,3,4, Rachel Simpson1,4, Rosalie A Carr1,4, Huangbing Wu1,4, Hao Fan5, Ziyue Liu6,7, Murray Korc3,8,9, Jianjun Zhang10,11, C Max Schmidt12,13,14,15,16. 1. Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive EH 129, Indianapolis, IN, 46202, USA. 2. Walther Oncology Center, Indianapolis, IN, USA. 3. Indiana University Simon Cancer Center, Indianapolis, IN, USA. 4. Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, USA. 5. Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, 1050 Wishard Blvd. RG5118, Indianapolis, IN, 46202, USA. 6. Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA. 7. Department of Biostatistics, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA. 8. Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA. 9. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. 10. Indiana University Simon Cancer Center, Indianapolis, IN, USA. JZ21@iu.edu. 11. Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, 1050 Wishard Blvd. RG5118, Indianapolis, IN, 46202, USA. JZ21@iu.edu. 12. Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive EH 129, Indianapolis, IN, 46202, USA. maxschmi@iupui.edu. 13. Walther Oncology Center, Indianapolis, IN, USA. maxschmi@iupui.edu. 14. Indiana University Simon Cancer Center, Indianapolis, IN, USA. maxschmi@iupui.edu. 15. Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, USA. maxschmi@iupui.edu. 16. Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA. maxschmi@iupui.edu.
Abstract
BACKGROUND: The most common type of mucinous pancreatic cyst that may progress to pancreatic cancer is intraductal papillary mucinous neoplasm (IPMN). Low-risk IPMN with low-/moderate-grade dysplasia may be safely watched, whereas high-risk IPMN with high-grade dysplasia or invasive components should undergo resection. However, there is currently no reliable means of making this distinction. We hypothesize that blood concentrations of insulin resistance biomarkers may aid in the differentiation of low- and high-risk IPMN. METHODS: Plasma/serum was collected from consented patients undergoing pancreatic resection. IPMN diagnosis and dysplastic grade were confirmed by surgical pathology. The study included 235 IPMN (166 low/moderate grade, 39 high grade, 30 invasive). Circulating levels of leptin, branched chain amino acids (BCAA), and retinol-binding protein-4 (RBP-4) were measured by enzyme-linked immunoassay and correlated with surgical pathology. RESULTS: Circulating leptin levels (mean ± SE) were significantly higher in patients with low/moderate IPMN than in high-grade/invasive IPMN (15,803 ± 1686 vs. 10,275 ± 1228 pg/ml; p = 0.0086). Leptin levels were positively correlated with BMI (r = 0.65, p < 0.0001) and were higher in females (p < 0.0001). Stratified analysis showed that mean leptin levels were significantly different between low/moderate and high/invasive IPMNs only in females (24,383 ± 2748 vs. 16,295 ± 2040 pg/ml; p = 0.020). Conversely, circulating BCAA levels were lower in low/moderate IPMN than in high-grade/invasive IPMN (0.38 ± 0.007 vs. 0.42 ± 0.01 mM; p = 0.011). No significant differences in RBP-4 levels were observed. CONCLUSIONS: Circulating leptin in females and BCAA correlates with IPMN dysplastic grade and, if combined with clinical characteristics, have the potential to improve clinical decision-making.
BACKGROUND: The most common type of mucinous pancreatic cyst that may progress to pancreatic cancer is intraductal papillary mucinous neoplasm (IPMN). Low-risk IPMN with low-/moderate-grade dysplasia may be safely watched, whereas high-risk IPMN with high-grade dysplasia or invasive components should undergo resection. However, there is currently no reliable means of making this distinction. We hypothesize that blood concentrations of insulin resistance biomarkers may aid in the differentiation of low- and high-risk IPMN. METHODS: Plasma/serum was collected from consented patients undergoing pancreatic resection. IPMN diagnosis and dysplastic grade were confirmed by surgical pathology. The study included 235 IPMN (166 low/moderate grade, 39 high grade, 30 invasive). Circulating levels of leptin, branched chain amino acids (BCAA), and retinol-binding protein-4 (RBP-4) were measured by enzyme-linked immunoassay and correlated with surgical pathology. RESULTS: Circulating leptin levels (mean ± SE) were significantly higher in patients with low/moderate IPMN than in high-grade/invasive IPMN (15,803 ± 1686 vs. 10,275 ± 1228 pg/ml; p = 0.0086). Leptin levels were positively correlated with BMI (r = 0.65, p < 0.0001) and were higher in females (p < 0.0001). Stratified analysis showed that mean leptin levels were significantly different between low/moderate and high/invasive IPMNs only in females (24,383 ± 2748 vs. 16,295 ± 2040 pg/ml; p = 0.020). Conversely, circulating BCAA levels were lower in low/moderate IPMN than in high-grade/invasive IPMN (0.38 ± 0.007 vs. 0.42 ± 0.01 mM; p = 0.011). No significant differences in RBP-4 levels were observed. CONCLUSIONS: Circulating leptin in females and BCAA correlates with IPMN dysplastic grade and, if combined with clinical characteristics, have the potential to improve clinical decision-making.
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