TY - JOUR
T1 - Association of iron metabolic enzyme hepcidin expression levels with the prognosis of patients with pancreatic cancer
AU - Toshiyama, Reishi
AU - Konno, Masamitsu
AU - Eguchi, Hidetoshi
AU - Asai, Ayumu
AU - Noda, Takehiro
AU - Koseki, Jun
AU - Asukai, Kei
AU - Ohashi, Tomofumi
AU - Matsushita, Katsunori
AU - Iwagami, Yoshifumi
AU - Yamada, Daisaku
AU - Asaoka, Tadafumi
AU - Wada, Hiroshi
AU - Kawamoto, Koichi
AU - Gotoh, Kunihito
AU - Kudo, Toshihiro
AU - Satoh, Taroh
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Ishii, Hideshi
N1 - Funding Information:
The present work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (grant nos. 17H04282, 17K19698; 16K15615 and 15H05791), a grant from P-DIRECT (grant no. 15cm0106105h0002; AMED-Japan Cancer Research Project).
Publisher Copyright:
© 2018, Spandidos Publications. All rights reserved.
PY - 2018/5
Y1 - 2018/5
N2 - Hepcidin and ferroportin, which are known as key iron regulators, may be used in future treatments of pancreatic ductal adenocarcinoma. Iron is essential for life support; it helps oxygen molecules bind to hemoglobin and acts as an important catalytic enzyme center. However, iron overload is a risk factor for cancer, possibly through the generation of reactive oxygen species (ROS). Hepcidin, which is a peptide hormone mainly generated by the liver, inhibits iron absorption via enterocytes and iron release from macrophages. Notably, hepcidin regulates iron homeostasis in the body by regulating the iron transporter ferroportin. In the present study, it was assumed that high hepcidin expression and low ferroportin expression result in malignancy. Therefore, it was examined whether hepcidin and ferroportin expression levels were correlated with the prognosis of pancreatic cancer in patients. Results revealed that high hepcidin expression levels and low ferroportin expression levels in pancreatic cancer tissue were significantly associated with poor prognosis in the analyses of overall survival (P=0.0140 and 0.0478, respectively). Additionally, there was no significant difference in disease-free survival in the hepcidin- and ferroportin-staining groups. Hepcidin expression correlated with the pathological stage and vascular invasion (P=0.0493 and 0.0400, respectively), and ferroportin expression was correlated with age (P=0.0372). Multivariate analysis of overall survival in the hepcidin-staining group revealed that pathological N factor (pN), adjuvant chemotherapy, and hepcidin expression were independent prognostic factors (P=0.0450, 0.0002, and 0.0049, respectively). Similarly, multivariate analysis of overall survival in the ferroportin-staining group revealed that vascular invasion, and ferroportin expression were independent prognostic factors (P=0.0028, P<0.0001, and P=0.0056, respectively). Thus, hepcidin and ferroportin expressions might be novel prognostic indicators for pancreatic cancer.
AB - Hepcidin and ferroportin, which are known as key iron regulators, may be used in future treatments of pancreatic ductal adenocarcinoma. Iron is essential for life support; it helps oxygen molecules bind to hemoglobin and acts as an important catalytic enzyme center. However, iron overload is a risk factor for cancer, possibly through the generation of reactive oxygen species (ROS). Hepcidin, which is a peptide hormone mainly generated by the liver, inhibits iron absorption via enterocytes and iron release from macrophages. Notably, hepcidin regulates iron homeostasis in the body by regulating the iron transporter ferroportin. In the present study, it was assumed that high hepcidin expression and low ferroportin expression result in malignancy. Therefore, it was examined whether hepcidin and ferroportin expression levels were correlated with the prognosis of pancreatic cancer in patients. Results revealed that high hepcidin expression levels and low ferroportin expression levels in pancreatic cancer tissue were significantly associated with poor prognosis in the analyses of overall survival (P=0.0140 and 0.0478, respectively). Additionally, there was no significant difference in disease-free survival in the hepcidin- and ferroportin-staining groups. Hepcidin expression correlated with the pathological stage and vascular invasion (P=0.0493 and 0.0400, respectively), and ferroportin expression was correlated with age (P=0.0372). Multivariate analysis of overall survival in the hepcidin-staining group revealed that pathological N factor (pN), adjuvant chemotherapy, and hepcidin expression were independent prognostic factors (P=0.0450, 0.0002, and 0.0049, respectively). Similarly, multivariate analysis of overall survival in the ferroportin-staining group revealed that vascular invasion, and ferroportin expression were independent prognostic factors (P=0.0028, P<0.0001, and P=0.0056, respectively). Thus, hepcidin and ferroportin expressions might be novel prognostic indicators for pancreatic cancer.
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U2 - 10.3892/ol.2018.8357
DO - 10.3892/ol.2018.8357
M3 - Article
AN - SCOPUS:85044655394
SN - 1792-1074
VL - 15
SP - 8125
EP - 8133
JO - Oncology Letters
JF - Oncology Letters
IS - 5
ER -
