Development of the multiplex diagnostic method able to make a definitive diagnosis of prostate cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K06858
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Juntendo University
• Principal Investigator: Kazuno Saiko 順天堂大学, 医学(系)研究科(研究院), 助教 (00338344)
• Co-Investigator(Kenkyū-buntansha): 上野 隆 順天堂大学, 医学(系)研究科(研究院), 客員教授 (10053373) ; 藤村 務 東北医科薬科大学, 薬学部, 教授 (70245778)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 前立腺がん / プロテオーム解析 / 糖鎖 / バイオマーカー / レクチン / 糖タンパク質 / マルチプレックス

Outline of Final Research Achievements

The purpose of our study is to develop a low invasive, definitive diagnostic method to overcome frequent errors of PSA, a widely used diagnostic marker for prostate cancer. Using lectin array, we first characterized glycosylation status of serum glycoproteins and found that 0-glycans were more enriched in patients’ sera. O-glycan-bearing serum glycoproteins were comprehensively collected using O-glycan-specific lectins and subsequently analyzed by the quantitative proteomic analysis. It was found that clusterin in malignant sera was more O-glycosylated than that in benign patients or control subjects. We further developed a new method to quantify O-glycosylated clusterin in the serum: serum clusterin that had been adsorbed on anti-clusterin IgG-immobilized fluorescent beads was probed with another fluorescent O-glycan-specific lectin beads using a Luminex 200. The method is more reliable to distinguish prostate cancer patients from benign prostate disease and healthy person.

Free Research Field

プロテオミクス解析

Academic Significance and Societal Importance of the Research Achievements

前立腺がんマーカーであるPSA値はがん特異性が低い問題点がありグレーゾーンといわれる範囲に悪性と良性患者が混在し、生検に依存しないPSA値を補完する低侵襲ながん診断法の確立が望まれる。本研究は抗体結合ビーズ‐レクチン検出法によるPSA値診断の問題克服を目指した。clusterinをターゲットとして開発した蛍光ビーズ結合抗体－レクチン検出法はROC分析から特にPSA値10ng/ml以下のグレーゾーン患者においてPSA値より優れた結果が得られた。本法は有意に前立腺がん患者を識別できることを確認し、PSA値による診断の問題点を補完する可能性が示唆された。