Association of iron metabolic enzyme hepcidin expression levels with the prognosis of patients with pancreatic cancer

Toshiyama,Reishi; Konno,Masamitsu; Eguchi,Hidetoshi; Asai,Ayumu; Noda,Takehiro; Koseki,Jun; Asukai,Kei; Ohashi,Tomofumi; Matsushita,Katsunori; Iwagami,Yoshifumi; Yamada,Daisaku; Asaoka,Tadafumi; Wada,Hiroshi; Kawamoto,Koichi; Gotoh,Kunihito; Kudo,Toshihiro; Satoh,Taroh; Doki,Yuichiro; Mori,Masaki; Ishii,Hideshi

doi:10.3892/ol.2018.8357

Association of iron metabolic enzyme hepcidin expression levels with the prognosis of patients with pancreatic cancer

Authors:
- Reishi Toshiyama
- Masamitsu Konno
- Hidetoshi Eguchi
- Ayumu Asai
- Takehiro Noda
- Jun Koseki
- Kei Asukai
- Tomofumi Ohashi
- Katsunori Matsushita
- Yoshifumi Iwagami
- Daisaku Yamada
- Tadafumi Asaoka
- Hiroshi Wada
- Koichi Kawamoto
- Kunihito Gotoh
- Toshihiro Kudo
- Taroh Satoh
- Yuichiro Doki
- Masaki Mori
- Hideshi Ishii
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Affiliations: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565‑0871, Japan, Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka 565‑0871, Japan, Department of Medical Data Science, Graduate School of Medicine, Osaka University, Suita, Osaka 565‑0871, Japan
Published online on: March 26, 2018 https://doi.org/10.3892/ol.2018.8357
Pages: 8125-8133

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Abstract

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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