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
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.
Oncol Lett. 2018 May;15(5):8125-8133. doi: 10.3892/ol.2018.8357. Epub 2018 Mar 26.
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.
铁调素和铁转运蛋白被认为是关键的铁调节因子，未来可能用于治疗胰腺导管腺癌。铁是维持生命所必需的；它有助于氧分子与血红蛋白结合，并作为重要的催化酶中心。然而，铁过载可能是癌症的一个危险因素，可能是通过产生活性氧（ROS）。铁调素是一种主要由肝脏产生的肽激素，它通过抑制肠细胞对铁的吸收以及巨噬细胞释放铁来发挥作用。值得注意的是，铁调素通过调节铁转运蛋白来调节体内的铁稳态。在本研究中，假设铁调素高表达和铁转运蛋白低表达会导致恶性肿瘤。因此，研究人员检测了铁调素和铁转运蛋白的表达水平是否与胰腺癌患者的预后相关。结果显示，在总生存分析中，胰腺癌组织中铁调素高表达水平和铁转运蛋白低表达水平与预后不良显著相关（分别为P = 0.0140和0.0478）。此外，铁调素和铁转运蛋白染色组的无病生存期没有显著差异。铁调素表达与病理分期和血管侵犯相关（分别为P = 0.0493和0.0400），铁转运蛋白表达与年龄相关（P = 0.0372）。铁调素染色组总生存的多因素分析显示，病理N因子（pN）、辅助化疗和铁调素表达是独立的预后因素（分别为P = 0.0450、0.0002和0.0049）。同样，铁转运蛋白染色组总生存的多因素分析显示，血管侵犯和铁转运蛋白表达是独立的预后因素（分别为P = 0.0028、P < 0.0001和P = 0.0056）。因此，铁调素和铁转运蛋白的表达可能是胰腺癌新 的预后指标。
