J Cancer 2018; 9(24):4736-4741. doi:10.7150/jca.25404

Research Paper

Angiopoietin-like Protein 2 is a Useful Biomarker for Pancreatic Cancer that is Associated with Type 2 Diabetes Mellitus and Inflammation

Takuma Yoshinaga1, Tatsuyuki Niou2, Toru Niihara2, Yoriko Kajiya 3, Emiko Hori1, Ayako Tomiyoshi1, Erena Tokudome1, Hiroto Nishimata2, Takayuki Takei4, Masahiro Yoshida4✉

1. Division of Clinical Application, Nanpuh Hospital, Kagoshima, Japan,
2. Gastroenterology, Nanpuh Hospital, Kagoshima, Japan,
3. Department of Radiology, Nanpuh Hospital, Kagoshima, Japan,
4. Department of Chemical Engineering, Graduate School of Science and Engineering, Kagoshima, Japan.

Abstract

Pancreatic cancer is one of the tumors with the worst prognosis, with the 5-year survival rate reported to be 6%. The number of patients suffering from pancreatic cancer in recent years has continued to increase dramatically. Carbohydrate antigen 19-9 is an established biomarker of pancreatic cancer, but it does not have sufficient ability to detect pancreatic cancer at an early stage. We focused on angiopoietin-like protein 2 (ANGPTL2), which has been reported to be related to chronic inflammation and Type 2 diabetes mellitus. In this study, whether ANGPTL2 can detect early pancreatic cancer was evaluated. It was found that the concentration of serum ANGPTL2 was significantly higher in pancreatic cancer patients and tumor stage 0-I patients than in healthy individuals (5.84 ± 1.82 ng/mL vs 3.61 ± 0.64 ng/mL; P < 0.001) (5.68 ± 0.79 ng/mL vs 3.61 ± 0.64 ng/mL; P = 0.010). In addition, the diagnostic capability of serum ANGPTL2 levels for pancreatic cancer was evaluated using receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC) for ANGPTL2 was 0.906 (95% confidence interval (CI): 0.815-0.997; P < 0.001). To identify the risk factors for pancreatic cancer, multivariate regression models were used. Ten factors were included, and increasing age (odds ratio (OR), 1.318, 95% CI, 1.058-1.642; P = 0.014) and high ANGPTL2 levels (OR, 22.219, 95% CI, 1.962-251.659, P = 0.012) were found to be independent risk factors for pancreatic cancer, with ANGPTL2 having the strongest relationship. In addition, serum ANGPTL2 levels were strongly correlated with inflammatory markers, with blood sugar levels showing the strongest correlation with serum ANGPTL2 levels. In conclusion, this study suggested that an elevated serum ANGPTL2 level has the potential to be a biomarker capable of early detection of pancreatic cancer, and it was correlated with inflammation of the pancreas and the risk of developing diabetes mellitus.

Keywords: ANGPTL2, biomarker, pancreatic cancer, mellitus, angiogenesis

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How to cite this article:
Yoshinaga T, Niou T, Niihara T, Kajiya Y, Hori E, Tomiyoshi A, Tokudome E, Nishimata H, Takei T, Yoshida M. Angiopoietin-like Protein 2 is a Useful Biomarker for Pancreatic Cancer that is Associated with Type 2 Diabetes Mellitus and Inflammation. J Cancer 2018; 9(24):4736-4741. doi:10.7150/jca.25404. Available from http://www.jcancer.org/v09p4736.htm