Mechanism of transportation of galectin-3 in extrahepatic bile duct cancer as a novel bio-maker for prognosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10605
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Fukushima Medical University
• Principal Investigator: Shimura Tatsuo 福島県立医科大学, 医学部, 教授 (00282393)
• Co-Investigator(Kenkyū-buntansha): 竹之下 誠一 福島県立医科大学, 医学部, 教授 (10167489)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: galectin-3 / 胆管癌

Outline of Final Research Achievements

In the analysis on immunohistochemistry of galectin-3 expressions in bile duct cancer patients, patients with nuclear expression of galectin-3 showed poorer prognosis than those without this expression. Patients with higher serum galectin-3 showed poorer prognosis in patients with extrahepatic bile duct cancer or pancreatic cancer. This was an independent prognostic factor in the patients by the Cox regression model. In the analysis using bile duct cancer cell line, HuCCT-1, the cells showed nuclear expression of galectin-3, when cultivated on the poly-HEME-coated dish. However, the inhibitor for GSK-3 beta or beta-catenin could not inhibit nuclear transportation, while these molecules have been reported to have some relationship with nuclear expression of galectin-3. The inhibitors for the immune checkpoint, PD-1/PD-L1, have also been reported some relationship between galectin families. However, the relationship between galectin-3 and PD-1/PD-L1 was not recognized in our study.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

肝外胆管癌は、いまだ予後不良であり、標準治療といわれるものが確立されていない。胆管癌切除標本において、galectin-3の免疫染色を行うと、癌先進部やリンパ節転移部、多臓器転移巣において癌細胞核内にgalectin-3が局在しており、この所見を認める症例は予後不良であることを報告した。胆管癌において血液中galectin-3濃度が高値（10.2 ng/ml以上）群では有意に予後不良であり、Cox比例ハザードモデルでは独立予後因子であった。今後の胆管癌治療において、galectin-3の核内発現が新たなバイオマーカーとなり得ることを報告できた。