Development of a new companion diagnostic for immune CP inhibitors for metastatic urothelial cancer using glycan analysis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09364
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Hirosaki University
• Principal Investigator: Hashimoto Yasuhiro 弘前大学, 医学研究科, 准教授 (60322939)
• Co-Investigator(Kenkyū-buntansha): 山本 勇人 弘前大学, 医学研究科, 准教授 (30532759) ; 米山 高弘 弘前大学, 医学部付属病院, 准教授 (90374834)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 糖鎖解析 / 尿路上皮癌 / 免疫CP阻害剤

Outline of Final Research Achievements

In recent years, there has been an increase in the use of immune checkpoint inhibitors for patients with metastatic urothelial carcinoma due to their inclusion in insurance coverage. While some cases have shown dramatic effectiveness, more than half exhibit insufficient response, underscoring the need for biomarkers to predict efficacy before treatment initiation. We have contemplated the development of biomarkers for predicting the efficacy of immune checkpoint inhibitors through comprehensive mass analysis of serum N-linked glycans.
Using the Gly-Q capillary electrophoresis system and machine learning with DataRobot, we identified two types of glycans from the 26 N-glycan structures in serum immunoglobulin fractions as potential candidates for assessing treatment efficacy. We plan to further investigate by increasing the number of cases in the future

Free Research Field

泌尿器腫瘍学

Academic Significance and Societal Importance of the Research Achievements

転移性の尿路上皮癌は予後不良の疾患である。免疫CP阻害剤はその転移性尿路上皮癌に使用されるが、非常に効果のある症例もある反面、半数以上は効果不十分である。今回の我々の検討では特徴的な糖鎖の変化と免疫CP阻害剤の治療効果が相関する可能性があることが示された。機器の普及など課題はあるが、本研究成果の学術的意義や社会的意義は非常に大きいと思われる。