Rachel E Simpson1, Michele T Yip-Schneider2, Huangbing Wu1, Hao Fan3, Ziyue Liu4, Murray Korc5, Jianjun Zhang6, C Max Schmidt7. 1. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indiana University School of Medicine, Indianapolis, IN, USA. 2. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Walther Oncology Center, Indianapolis, IN, USA; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indiana University School of Medicine, Indianapolis, IN, USA. 3. Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA. 4. Department of Biostatistics, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA. 5. Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA; The Pancreatic Cancer Signature Center at IUPUI, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA. 6. Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA. Electronic address: JZ21@iu.edu. 7. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Walther Oncology Center, Indianapolis, IN, USA; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: maxschmi@iupui.edu.
Abstract
BACKGROUND: IPMNs are cystic pancreatic lesions with variable malignant potential. Thrombospondin-2 (THBS2)-an endogenous, anti-angiogenic matrix glycoprotein-may modulate tumor progression. We hypothesized that circulating levels of THBS2 could aid in preoperative prediction of malignant IPMN. METHODS: Preoperative serum/plasma samples were procured from patients undergoing surgery. Circulating levels of THBS2 were measured (enzyme-linked immunosorbent assay) and compared to surgical pathology IPMN dysplastic grade. RESULTS: 164 patients underwent THBS2 testing (100 Low/Moderate-IPMN; 64 High-Grade/Invasive-IPMN). Circulating THBS2 (mean ± SD) was greater in High-Grade/Invasive-IPMN than Low/Moderate-grade IPMN (26.6 ± 12.7 ng/mL vs. 20.4 ± 8.2 ng/mL; P < 0.001). THBS2 (AUC = 0.65) out-performed CA19-9 (n = 144; AUC = 0.59) in predicting IPMN grade. The combination of THBS2, CA19-9, radiographic main-duct involvement, main-duct diameter, age, sex, and BMI (AUC 0.82; n = 137) provided a good prediction model for IPMN grade. CONCLUSION: Circulating THBS2 is correlated with IPMN dysplasia grade. THBS2 alone did not strongly predict IPMN grade but rather strengthened prediction models for High-Grade/Invasive IPMN when combined with other clinical/biomarker data.
BACKGROUND: IPMNs are cystic pancreatic lesions with variable malignant potential. Thrombospondin-2 (THBS2)-an endogenous, anti-angiogenic matrix glycoprotein-may modulate tumor progression. We hypothesized that circulating levels of THBS2 could aid in preoperative prediction of malignant IPMN. METHODS: Preoperative serum/plasma samples were procured from patients undergoing surgery. Circulating levels of THBS2 were measured (enzyme-linked immunosorbent assay) and compared to surgical pathology IPMN dysplastic grade. RESULTS: 164 patients underwent THBS2 testing (100 Low/Moderate-IPMN; 64 High-Grade/Invasive-IPMN). Circulating THBS2 (mean ± SD) was greater in High-Grade/Invasive-IPMN than Low/Moderate-grade IPMN (26.6 ± 12.7 ng/mL vs. 20.4 ± 8.2 ng/mL; P < 0.001). THBS2 (AUC = 0.65) out-performed CA19-9 (n = 144; AUC = 0.59) in predicting IPMN grade. The combination of THBS2, CA19-9, radiographic main-duct involvement, main-duct diameter, age, sex, and BMI (AUC 0.82; n = 137) provided a good prediction model for IPMN grade. CONCLUSION: Circulating THBS2 is correlated with IPMN dysplasia grade. THBS2 alone did not strongly predict IPMN grade but rather strengthened prediction models for High-Grade/Invasive IPMN when combined with other clinical/biomarker data.
Authors: Tessa Y S Le Large; Laura L Meijer; Elisa Giovannetti; Geert Kazemier; Rosita Paleckyte; Lenka N C Boyd; Bart Kok; Thomas Wurdinger; Tim Schelfhorst; Sander R Piersma; Thang V Pham; Nicole C T van Grieken; Barbara M Zonderhuis; Freek Daams; Hanneke W M van Laarhoven; Maarten F Bijlsma; Connie R Jimenez Journal: Oncologist Date: 2020-01-14
Authors: Furqan Aziz; Animesh Acharjee; John A Williams; Dominic Russ; Laura Bravo-Merodio; Georgios V Gkoutos Journal: Int J Mol Sci Date: 2020-10-23 Impact factor: 5.923