JP5443156B2 - 前立腺癌を判定する方法 - Google Patents
前立腺癌を判定する方法 Download PDFInfo
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- JP5443156B2 JP5443156B2 JP2009298794A JP2009298794A JP5443156B2 JP 5443156 B2 JP5443156 B2 JP 5443156B2 JP 2009298794 A JP2009298794 A JP 2009298794A JP 2009298794 A JP2009298794 A JP 2009298794A JP 5443156 B2 JP5443156 B2 JP 5443156B2
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- psa
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- prostate cancer
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Description
[1]
被験者由来の試料中のPSAの糖鎖構造を分析する工程を含み、LacdiNAc(N−アセチルガラクトサミン−N−アセチルグルコサミン)を有する3本鎖以上の糖鎖が存在するときに前立腺癌であると判定することを特徴とする前立腺癌を判定する方法。
[2]
上記PSAの糖鎖構造の分析を、上記PSAに対してレクチンを作用させる方法、上記PSAに対して抗体を作用させる方法、高速液体クロマトグラフィー法もしくは質量分析法、またはこれらを組み合わせた分析手段により行うことを特徴とする[1]に記載の前立腺癌を判定する方法。
[3]
(1)被験者由来の試料からPSAを精製する工程と、
(2)工程(1)で精製したPSAからPSA誘導体を調製する工程と、
(3)工程(2)で得られたPSA誘導体を標識する工程と、
(4)工程(3)で得られた標識化PSA誘導体を質量分析法により分析する工程を含み、LacdiNAcを有する3本鎖以上の糖鎖が存在するときに前立腺癌であると判定することを特徴とする[2]に記載の前立腺癌を判定する方法。
[4]
上記工程(2)において調製されるPSA誘導体が、PSA由来の糖鎖であることを特徴とする[3]に記載の前立腺癌を判定する方法。
[5]
上記工程(2)において調製されるPSA誘導体が、PSA由来の糖ペプチドであることを特徴とする[3]に記載の前立腺癌を判定する方法。
[6]
上記工程(1)で精製されたPSAに対し、コンカナバリンAレクチン(ConA)を接触させることによって、該PSAの中からConAに結合する糖鎖構造を有するPSAを除去し、ConAに結合しない糖鎖構造を有するPSAを得る工程を含み、上記工程(2)においては、該工程で得られたConAに結合しない糖鎖構造を有するPSAからPSA誘導体を調製することを特徴とする[3]に記載の前立腺癌を判定する方法。
[7]
上記工程(2)で調製されたPSA誘導体に対し、コンカナバリンAレクチン(ConA)を接触させることによって、該誘導体の中からConAに結合する糖鎖構造を有するPSA誘導体を除去し、ConAに結合しない糖鎖構造を有するPSA誘導体を得る工程を含み、上記工程(3)においては、該工程で得られたConAに結合しない糖鎖構造を有するPSA誘導体を標識することを特徴とする[3]に記載の前立腺癌を判定する方法。
[8]
下記式(1)で表される糖ペプチドを有することを特徴とする単離されたPSA。
GalNAc−GlcNAc− (a)
[式(a)中、「Gal」はガラクトースを示し、「Glc」はグルコースを示し、「Ac」はアセチル基を示し、「NAc」で、グルコサミン又はガラクトサミンのN(窒素原子)にアセチル基が結合していることを示す。]
Gal−GlcNAc− (b)
[式(b)中、「Gal」はガラクトースを示し、「Glc」はグルコースを示し、「Ac」はアセチル基を示し、「GlcNAc」で、グルコサミンのN(窒素原子)にアセチル基が結合していることを示す。]
*上記PSAに対してレクチンを作用させる方法、
*上記PSAに対して抗体を作用させる方法、
*高速液体クロマトグラフィー法、もしくは、
*質量分析法、
または、
*これらを組み合わせた分析手段
により行うことが好ましい。
(1)被験者由来の試料からPSAを精製する工程と、
(2)工程(1)で精製したPSAからPSA誘導体を調製する工程と、
(3)工程(2)で得られたPSA誘導体を標識する工程と、
(4)工程(3)で得られた標識化PSA誘導体を質量分析法により分析する工程と、
を含み、
LacdiNAc(N−アセチルガラクトサミン−N−アセチルグルコサミン)を有する3本鎖以上の糖鎖が存在するときに、すなわちLacdiNAcを有する3本鎖以上の糖鎖を検出したときに、前立腺癌であると判定する方法である。
生検によりPCと診断され、識別コードを付した1名の被験者(N−315)の血清(337.9ng PSA/mL)を用いた。なお、手順の実施に際し医療機関の倫理審査の承認を受け、被験者にはインフォームドコンセントを行なった。
最初に血清から免疫グロブリンの除去を行った。5mLのプロテインAアガロース担体(PIERCE)をリン酸緩衝生理食塩水(PBS)で平衡化した。これをディスポーザブルプラスティックカラム(PIERCE)に充填し、該被験者の血清およびPBSの混合物を添加し、4℃にて30分間振盪した。この担体に結合しないPSAを含む画分を回収し、さらに担体の3倍体積(3CV)のPBSにてプロテインAアガロース担体を洗浄した画分を回収後、両画分の混合溶液に最終濃度が1MになるようにNa2SO4を加えた。
工程(a)で得られた減圧乾固サンプルの入ったチューブに対して、50単位のサーモリシン(Calbio)を含む50mM炭酸水素アンモニウム水溶液(pH8.0)、100μLを直接加え、18時間にわたって56℃で静置反応させた。反応混合物を遠心濃縮機によって乾固させた後、得られた固形物を、0.8%トリフルオロ酢酸水溶液に溶解し、40分間にわたって80℃で静置し、脱シアル酸反応を行った。反応サンプルを遠心濃縮機で乾固させた。
MALDI用ターゲットプレートの上に、工程2で得られた糖ペプチド溶液1.0μLを滴下し、風乾させた。次に、ターゲットプレート上に、1−ピレニルジアゾメタン(PDAM、500pmol)のDMSO溶液0.25μLを滴下し、約5分間にわたって80℃に加熱し、乾燥させた。この操作によって、ターゲットプレート上に、PDAMで標識された糖ペプチドが得られた。
工程3で得られた標識糖ペプチドを担持したターゲットプレートに対して、2,5−ジヒドロキシ安息香酸(DHBA)の60%アセトニトリル溶液(濃度10mg/mL)1.0μLを滴下し、室温において乾燥させた。
実施例1で使用したサンプルと同じ血清を対象に、工程1、工程2のサーモリシン反応および脱シアル酸反応を実施した後に、固相化コンカナバリンA(ConA)担体を使用し、担体に結合しない画分を調製することで、3本鎖以上の糖鎖を選択的に検出した。
実施例1で使用したサンプルと同じ血清を対象に、工程1を実施した後に、固相化コンカナバリンA(ConA)担体を使用し、担体に結合しない画分を調製することで、式(1)で表される糖ペプチドを有するPSAを選択的に単離できる。
Claims (6)
- 被験者由来の試料中のPSAの糖鎖構造を分析する工程を含み、LacdiNAc(N−アセチルガラクトサミン−N−アセチルグルコサミン)を有する3本鎖以上の糖鎖が存在するときに前立腺癌であると判定することを特徴とする前立腺癌を判定する方法。
- 上記PSAの糖鎖構造の分析を、上記PSAに対してレクチンを作用させる方法、上記PSAに対して抗体を作用させる方法、高速液体クロマトグラフィー法もしくは質量分析法、またはこれらを組み合わせた分析手段により行うことを特徴とする請求項1に記載の前立腺癌を判定する方法。
- (1)被験者由来の試料からPSAを精製する工程と、
(2)工程(1)で精製したPSAからPSA誘導体を調製する工程と、
(3)工程(2)で得られたPSA誘導体を標識する工程と、
(4)工程(3)で得られた標識化PSA誘導体を質量分析法により分析する工程を含み、LacdiNAc(N−アセチルガラクトサミン−N−アセチルグルコサミン)を有する3本鎖以上の糖鎖が存在するときに前立腺癌であると判定することを特徴とする請求項2に記載の前立腺癌を判定する方法。 - 上記工程(2)において調製されるPSA誘導体が、PSA由来の糖鎖または糖ペプチドであることを特徴とする請求項3に記載の前立腺癌を判定する方法。
- 上記工程(1)で精製されたPSAに対し、コンカナバリンAレクチン(ConA)を接触させることによって、該PSAの中からConAに結合する糖鎖構造を有するPSAを除去し、ConAに結合しない糖鎖構造を有するPSAを得る工程を含み、上記工程(2)においては、該工程で得られたConAに結合しない糖鎖構造を有するPSAからPSA誘導体を調製することを特徴とする請求項3に記載の前立腺癌を判定する方法。
- 上記工程(2)で調製されたPSA誘導体に対し、コンカナバリンAレクチン(ConA)を接触させることによって、該誘導体の中からConAに結合する糖鎖構造を有するPSA誘導体を除去し、ConAに結合しない糖鎖構造を有するPSA誘導体を得る工程を含み、上記工程(3)においては、該工程で得られたConAに結合しない糖鎖構造を有するPSA誘導体を標識することを特徴とする請求項3に記載の前立腺癌を判定する方法。
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