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JNCI-J. Natl. Cancer Inst., Published: 06 October 2021 | https://doi.org/10.1093/jnci/djab191 A Serum Marker for Early Pancreatic Cancer with a Possible Link to Diabetes

Hoonsik Nam, PharmD,^1,† Soon-Sun Hong, PhD,^2,† Kyung Hee Jung, PhD,^2,† Sunmi Kang, PhD,^1,† Min Seok Park, BS,^2,† Suyeon Kang, MS,³ Han Sun Kim, PharmD,¹ Van-Hieu Mai, MD,¹ Juyoung Kim, MS,² Ho Lee, PhD,⁴ Woohyung Lee, MD,⁵ Young Ju Suh, PhD,² Joo Han Lim, MD,⁶ Soo-Youl Kim, PhD,⁷ Song Cheol Kim, MD, PhD,⁵ So Hun Kim, MD, PhD,⁸ Sunghyouk Park, PhD^1,*

¹Natural Product Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea; ²Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science and Engineering, Inha University, Incheon, Korea; ³Department of Statistics, College of Natural Sciences, Inha University, Incheon, Korea; ⁴Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea; ⁵Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; ⁶Division of Hematology and Oncology, Department of Internal Medicine, Inha University Hospital, Inha University, Incheon, Korea; ⁷Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Korea; and ⁸Department of Endocrinology and Metabolism, Department of Internal Medicine, Inha University Hospital, Inha University, Incheon, Korea

^†These authors contributed equally to this work.
^*Correspondence to: Sunghyouk Park, PhD

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 subjects) 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 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).

Conclusion
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.

논문정보

형식Research article
게재일2021년 10월 (BRIC 등록일 2021-10-22)
연구진국내 연구진
분야 생명과학 > 생화학

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