A Serum Marker for Early Pancreatic Cancer With a Possible Link to Diabetes

Author:

Nam Hoonsik1ORCID,Hong Soon-Sun2,Jung Kyung Hee2ORCID,Kang Sunmi1,Park Min Seok2ORCID,Kang Suyeon3,Kim Han Sun1,Mai Van-Hieu1,Kim Juyoung2,Lee Ho4ORCID,Lee Woohyung5,Suh Young Ju2ORCID,Lim Joo Han6,Kim Soo-Youl7,Kim Song Cheol5ORCID,Kim So Hun8ORCID,Park Sunghyouk1ORCID

Affiliation:

1. Natural Product Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea

2. Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science and Engineering, Inha University, Incheon, Korea

3. Department of Statistics, College of Natural Sciences, Inha University, Incheon, Korea

4. Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea

5. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

6. Division of Hematology and Oncology, Department of Internal Medicine, Inha University Hospital, Inha University, Incheon, Korea

7. Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Korea

8. Department of Endocrinology and Metabolism, Department of Internal Medicine, Inha University Hospital, Inha University, Incheon, Korea

Abstract

Abstract Background Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well established. Methods Bioinformatics screening was performed for a serum PC marker. Experiments in cell lines (5 PC and 1 normal cell lines), mouse models, and human tissue staining (37 PC and 10 normal cases) were performed to test asprosin production from PC. Asprosin’s diagnostic performance was tested with serums from multi-center cohorts (347 PC, 209 normal, and 55 additional diabetic patients) and evaluated according to PC status, stages, and diabetic status, which was compared with that of CA19-9. Results Asprosin, a diabetes-related hormone, was found from the bioinformatics screening, and its production from PC was confirmed. Serum asprosin levels from multi-center cohorts yielded an age-adjusted diagnostic area under the curve (AUC) of 0.987 (95% confidence interval [CI] = 0.961 to 0.997), superior to that of CA19-9 (AUC = 0.876, 95% CI = 0.847 to 0.905), and a cut-off of 7.18 ng/mL, at which the validation set exhibited a sensitivity of 0.957 and a specificity of 0.924. Importantly, the performance was maintained in early-stage and non-metastatic PC, consistent with the tissue staining. A slightly lower performance against additional diabetic patients (n = 55) was restored by combining asprosin and CA19-9 (AUC = 0.985, 95% CI = 0.975 to 0.995). Conclusions Asprosin is presented as an early-stage PC serum marker that may provide clues for PC-induced diabetes. Larger prospective clinical studies are warranted to solidify its utility.

Funder

National Research Foundation of Korea

Korea government Ministry of Science and ICT

Korean Health Technology R&D Project

Ministry of Health and Welfare

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

Reference33 articles.

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4. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal;Ballehaninna;J Gastrointest Oncol,2012

5. Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials;Bauer;Cancer,2013

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