Associations between MUC1 and PD-L1 in micropapillary variant of bladder cancer

Research Project

Project/Area Number	18K16688
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 56030:Urology-related
Research Institution	University of Fukui
Principal Investigator	Shinagawa Tomochika 福井大学, 学術研究院医学系部門, 特別研究員 (00610453)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	糖鎖発現 / 微小乳頭型膀胱癌 / 腎癌 / 癌免疫療法 / 糖鎖発現解析 / 膀胱癌
Outline of Final Research Achievements	In this study, we performed expression and functional analysis of carbohydrate antigen, Sialyl-Lewis x (sLeX) and Sialyl-Lewis a (sLeA), focusing on cell adhesion factors using specimens of the micropapillary variant of bladder cancer and renal cancer. Analysis for bladder cancer has not been completed due to the small number of cases. Analysis using surgical specimens of renal cancer revealed that sLeX/sLeA was expressed on the plasma membrane of cancer cells. Moreover, in in situ analysis, these sLeX/sLeA-positive ccRCC tissues were decorated with E-selectin-IgM chimeric proteins. Membrane expression of functional E-selectin ligand carbohydrates, as detected by the E-selectin-IgM chimera, correlated more significantly with poor prognosis of patients. Expression of E-selectin-IgM-binding functional E-selectin ligand carbohydrates can serve as a reliable and potentially superior prognostic biomarker of patients with ccRCC.
Academic Significance and Societal Importance of the Research Achievements	癌組織の糖鎖発現は腫瘍微小環境で癌が浸潤、転移をきたす機序として注目されている。本研究では当初目標とした微小乳頭型膀胱癌での検討は不十分となったが、平行して行った腎癌の検討では、癌細胞における糖鎖(sLeX/sLeA)発現の有無や細胞接着因子であるE-selectinとの結合能評価を行い、腎癌の浸潤、転移との関連性を明らかにした。とくにE-selectin-IgMキメラ蛋白を用いた病理学的評価は、腎癌の新たな予後因子として有用であると考えられる。