Research Papers:

Increased serum levels of betatrophin in pancreatic cancer-associated diabetes

Hendra Susanto _, Ta-Yu Liu, Chang-Chiang Chen, Jerry D.T. Purnomo, Shu-Fan Chen and Chih-Hong Wang

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Oncotarget. 2016; 7:42330-42339. https://doi.org/10.18632/oncotarget.9815

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Hendra Susanto1,*, Ta-Yu Liu1,*, Chang-Chiang Chen1,2,*, Jerry D.T. Purnomo3, Shu-Fan Chen1, Chih-Hong Wang1

1Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan

2Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 300, Taiwan

3Institute of Statistics, National Chiao Tung University, Hsinchu 300, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Chih-Hong Wang, email: chihhong@nctu.edu.tw

Keywords: betatrophin, diabetes, insulin resistance, glucose intolerance, pancreatic cancer

Received: December 13, 2015     Accepted: May 20, 2016     Published: June 3, 2016


Long-standing diabetes or glucose intolerance is recognized as a crucial event in the process of pancreatic cancer. Betatrophin, a novel liver-derived hormone, promotes β-cell proliferation and improves glucose intolerance. However, the relationship between betatrophin and PDAC-associated diabetes is not fully understood. To evaluate the serum betatrophin levels in PDAC-associated diabetes, a total 105 Taiwanese subjects including 15 healthy subjects, and 12 patients having PDAC with normal glucose tolerance (PDAC-NGT), 12 patients having PC with impaired glucose tolerance (PDAC-IGT), and 66 patients having PC with diabetes mellitus (PDAC-DM) were enrolled for this study. Serum betatrophin and carbohydrate antigen 19-9 (CA19-9) levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Compared to healthy subjects, PDAC patients had higher levels of betatrophin and CA19-9. Consistently, betatrophin protein was significantly expressed in pancreatic ductal of PDAC-associated DM patients using immunohistochemistry (IHC) method. Furthermore, multivariate regression analysis showed the betatrophin was significantly and positively independent with T category (β= 0.605, P=0.010), serum albumin (β= 0. 423, P=0.021), lipase (β= 0.292, P=0.039), and blood urea nitrogen (BUN) (β= 0.303, P=0.040). Further, the betatrophin was three folds of having PDAC-associated diabetes with the highest odds ratio [OR=3.39; 95% CI (1.20–9.57); P=0.021) and receiver operating characteristic (ROC) curve analysis showed that AUC value of betarophin was 0.853 which is slightly larger than AUC value of CA19-9 (0.792) in PDAC-DM patients. Interestingly, AUC value of betarophin plus CA19-9 was 0.988 in PDAC-DM patients. Therefore, betatrophin combined CA19-9 may serve as a potential biomarker for PDAC-associated diabetes.

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