Expression profile and prognostic value of NNMT in patients with pancreatic cancer
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Yong Xu1,3*, Ping Liu2*, Dong-Hui Zheng3, Nan Wu4, Lun Zhu5, Changying Xing6, Jin Zhu1,7
1Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, China
2Department of Pathology, Shiyan Taihe Hospital, Hubei University of Medicine, Shiyan City, China
3Department of Nephrology, the Affiliated Huai’an Hospital of Xuzhou Medical College, Huai'an, China
4Department of Pathology, Jinling Hospital, Nanjing, China
5Department of Pathology, the Affiliated Huai’an Hospital of Xuzhou Medical College, Huai'an, China
6Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
7Huadong Medical Institute of Biotechniques, Nanjing, China
*These authors contributed equally to this work
Jin Zhu, e-mail: [email protected]
Changying Xing, e-mail: [email protected]
Keywords: pancreatic cancer, nicotinamide N-methyltransferase, clinicopathological features, overall survival
Received: November 22, 2015 Accepted: February 09, 2016 Published: March 03, 2016
The elevation of Nicotinamide N-methyltransferase (NNMT) has been reported in pancreatic cancer tissues and cell lines, but its clinical and prognostic implications remain controversial. This study aimed at investigating the expression of NNMT in pancreatic benign and malignant tissues and the prognostic value of NNMT in pancreatic cancer. The expression of NNMT in tissue specimens of 28 chronic pancreatitis patients and 178 pancreatic cancer patients were assayed with immunohistochemistry on tissue microarray. The NNMT expression levels of pancreatic patients were correlated with their clinicopathological characteristics. The influences of NNMT expression and patients’ clinicopathological characteristics on overall survival (OS) were analyzed. The percentage of NNMT high expression (NNMTh) in pancreatic cancer (55.6%) was significantly higher than those in chronic pancreatitis (21.4%) and paracancerous tissues (14.8%) (p < 0.001). NNMTh tends to significantly correlate with unfavorable clinicopathological features such as age > 60 years old (p = 0.014), tumor diameter > 4 cm (p < 0.001), TNM stage III or IV (p < 0.001) and poor tumor differentiation (p = 0.004). The median OS of patients with NNMTh and NNMTl were 7.0 months (95% CI: 5.275–8.725) and 11.5 months (95% CI: 9.759–13.241) respectively (p = 0.005). On multivariate analysis, NNMTl (hazards ratio [HR]: 0.399; 95% CI: 0.284–0.560; p < 0.001), absence of neurological involvement (HR: 0.651; 95% CI: 0.421–0.947; p = 0.041), TNM stage I or II (HR: 0.506; 95% CI: 0.299–0.719; p = 0.015) and well tumor differentiation (HR: 0.592; 95% CI: 0.319–0.894; p = 0.044) were significant favorable prognostic factors of OS. In conclusion, NNMT is upregulated in pancreatic cancer, correlates with unfavorable clinicopathological features and may serve as an independent prognosticator of patients’ survival.
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