Abstract
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.
Highlights
Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive human cancers, is the fourth leading cause of cancer-related deaths in the United States [1]
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 area under the curve (AUC) value of betarophin was 0.853 which is slightly larger than AUC value of carbohydrate antigen 19-9 (CA19-9) (0.792) in PDAC-Diabetes Mellitus (DM) patients
The aim of this study is to investigate the relationship between serum betatrophin concentrations and PDAC with or without glucose intolerance, and to determine whether betatrophin levels can serve as a biomarker for PDAC-associated diabetes
Summary
Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive human cancers, is the fourth leading cause of cancer-related deaths in the United States [1]. Most PDAC patients are diagnosed at an advanced stages, and only 10% to 20% of patients are resectable at the time of presentation [4]. Based on human epidemiologic and animal studies, most PDAC patients have glucose intolerance [5] and about. 80% of PDAC patients are either glycemic or diabetic and this exists in the pre-symptomatic phase [6]. PDACassociated diabetes can occur at a resectable stage, while resection of pancreatic tumor improves glucose intolerance [7]. Discovery of novel biomarkers for PDACassociated diabetes may apply for diagnosis of resectable PDAC at early stages
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