JP2019516104A - 子宮内膜がんのマーカーとしてのmmp9 - Google Patents
子宮内膜がんのマーカーとしてのmmp9 Download PDFInfo
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- JP2019516104A JP2019516104A JP2018557905A JP2018557905A JP2019516104A JP 2019516104 A JP2019516104 A JP 2019516104A JP 2018557905 A JP2018557905 A JP 2018557905A JP 2018557905 A JP2018557905 A JP 2018557905A JP 2019516104 A JP2019516104 A JP 2019516104A
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- G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
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Abstract
Description
a)対象の女性生殖器から得る液体試料におけるPERM、OSTP、CTNB1、CAYP1、XPO2、NGAL、SG2A1、CADH1、SPIT1、MMP9、NAMPT、LDHA、CASP3、PRDX1、MIF、K2C8、CAPG、MUC1、ANXA1、HSPB1、PIGR、CH10、CD44、CLIC1、TPIS、GSTP1、及びGTR1からなる群から選択される1以上のタンパク質の発現レベルをインビトロで判定すること、並びに
b)ステップ(a)のレベルを基準対照レベルと比較することであって、ステップ(a)で判定されたレベルが基準対照レベルよりも高い場合、それは対象が子宮内膜癌に罹患している疑いがあることを示すこと、
を含む。
a)対象の女性生殖器から得る液体試料におけるPERM、OSTP、CTNB1、CAYP1、XPO2、NGAL、SG2A1、CADH1、SPIT1、MMP9、NAMPT、LDHA、CASP3、PRDX1、MIF、K2C8、CAPG、MUC1、ANXA1、HSPB1、PIGR、CH10、CD44、CLIC1、TPIS、GSTP1、及びGTR1からなる群から選択される1以上のタンパク質の発現レベルをインビトロで判定するステップ、並びに
b)試験試料のタンパク質レベルが基準対照レベルよりも高い場合、子宮内膜癌と診断するか、対象が子宮内膜癌に罹患している疑いがあるかどうかを判定するステップ、
を含み、
i)対象が子宮内膜癌に罹患していると診断された場合又は子宮内膜癌に罹患した疑いがある場合、医療レジメンの開始が推奨され、
ii)患者が子宮内膜癌に罹患していないと診断された場合、医師による患者の検査結果を考慮して任意選択にフォローアップを行う
方法を提供する。
(a)医療レジメンの投与に先立ち、対象の女性生殖器から得る液体試料におけるPERM、OSTP、CTNB1、CAYP1、XPO2、NGAL、SG2A1、CADH1、SPIT1、MMP9、NAMPT、LDHA、CASP3、PRDX1、MIF、K2C8、CAPG、MUC1、ANXA1、HSPB1、PIGR、CH10、CD44、CLIC1、TPIS、GSTP1、及びGTR1からなる群から選択される1以上のタンパク質の発現レベルをインビトロで測定するステップ、
(b)医療レジメンの投与を開始したら、対象の女性生殖器から得る液体試料における当該のマーカーのレベルをインビトロで測定するステップ、並びに
(c)ステップ(b)で測定されたレベルがステップ(a)で測定されたレベルよりも低い場合には、医療レジメンが子宮内膜癌の治療に有効であることを示すように、ステップ(a)及び(b)で測定されたレベルを比較するステップ
を含む方法、あるいは
(i)医療レジメンの投与を開始させたら対象の女性生殖器から得る液体試料におけるPERM、OSTP、CTNB1、CAYP1、XPO2、NGAL、SG2A1、CADH1、SPIT1、MMP9、NAMPT、LDHA、CASP3、PRDX1、MIF、K2C8、CAPG、MUC1、ANXA1、HSPB1、PIGR、CH10、CD44、CLIC1、TPIS、GSTP1、及びGTR1からなる群から選択される1以上のタンパク質の発現レベルをインビトロで測定するステップ、並びに
(ii)ステップ(i)で測定されたレベルをマーカーの基準対照レベルと比較するステップ、
を含み、
ステップ(i)で測定されたレベルが基準対照レベルほど高くない場合、それは、医療レジメンが子宮内膜癌の治療に有効であることを示す方法を提供する。
a)子宮吸引液試料のMMP9の発現レベルをインビトロで判定すること、及び
b)ステップ(a)のレベルを基準対照レベルと比較することであって、ステップ(a)で判定されたレベルが基準対照レベルよりも高い場合、それは対象が子宮内膜癌に罹患している疑いがあることを示すことを含む方法;
a)子宮吸引液試料におけるMMP9の発現レベルをインビトロで判定するステップ、及び
b)試験試料のタンパク質レベルが基準対照レベルよりも高い場合、子宮内膜癌と診断するか、対象が子宮内膜癌に罹患している疑いがあるかどうかを判定するステップ
を含み、
i)対象が子宮内膜癌に罹患していると診断された場合又は子宮内膜癌に罹患している疑いがある場合、医療レジメンの開始が推奨され、
ii)患者が子宮内膜癌に罹患していないと診断された場合、医師による患者の検査結果を考慮して任意選択にフォローアップを行う
方法;並びに
(a)医療レジメンの投与に先立ち対象の女性生殖器から単離された子宮吸引液試料におけるMMP9の発現レベルをインビトロで判定するステップ、
(b)医療レジメンの投与を開始したら、対象の女性生殖器から得る単離された子宮吸引液試料における当該のマーカーのレベルをインビトロで測定するステップ、及び
(c)ステップ(b)で測定されたレベルがステップ(a)で測定されたレベルよりも低い場合には、医療レジメンが子宮内膜癌の治療に有効であることを示すように、ステップ(a)及び(b)で測定されたレベルを比較するステップ
を含む方法、あるいは
(i)医療レジメンの投与を開始させたら対象の女性生殖器から得る単離された子宮吸引液試料におけるMMP9の発現レベルをインビトロで判定するステップ、及び
(ii)ステップ(i)で測定されたレベルをマーカーの基準対照レベルと比較するステップ
を含み、
ステップ(i)で測定されたレベルが基準対照レベルほど高くない場合、それは、医療レジメンが子宮内膜癌の治療に有効であることを示す方法
を、提供する。
Albumin and IgG Depletion SpinTrapカラムを、GE Healthcare(カタログ番号28−9480−20)から購入した。Lys CエンドプロテイナーゼMSグレードは、Thermo Scientificから購入した(カタログ番号90051)。Watersから固相抽出カートリッジ、Sep Pak tC18、50mgを得た(カタログ番号WAT054960)。全ての他の試薬はSigma−Aldrichから得た。
2012年〜2015年にかけて、Vall d’Hebron大学病院(スペイン、バルセロナ)で、本前向き試験に参加する合計38人の患者(ECに苛まれている20人の女性と非ECの対照18人、即ちECの症状を有するがECと診断されなかった女性)が集められた。Vall d’Hebron倫理委員会によって承認された同意説明文書に、全ての患者が署名した(承認番号:PR_AMI_50−2012)。
20人のEC患者及び18人の非EC対照から得た子宮吸引物の上清を超音波処理して潜在性微小胞、タンパク質凝集体、及び/又は粘液を、5秒間に100%の振幅で5サイクルで破壊した(Labsonic M)。次いで、製造者の指示に従ってAlbumin&IgG Depletion Spin Trapキットを使用して、アルブミン及び免疫グロブリンGを50μlの上清試料から枯渇させた。全タンパク質濃度は、3回実施したBradfordアッセイによって測定した。次いで38試料の各々を25μgの2つのアリコートに分離して、全プロセスについて複製を生成したが、複製するには材料の量が不十分であった1つの試料を除いた。試料を重炭酸アンモニウムの50mM溶液に希釈して120μlの最終容量にし、50mMの重炭酸アンモニウム中に懸濁した185μlの10Mの尿素を添加することにより変性させ、22℃で20分間撹拌しながらインキュベートし、続いて超音波に浸して(Branson5510)10分間インキュベートした。次いで、試料を200mMジチオスレイトール7.8μlで37℃で60分間還元し、22℃で12.2μlの400mMヨードアセトアミドで暗所で30分間アルキル化した。試料をLys C(プロテアーゼ/総タンパク質量比1/150;w/w)で37℃で4時間消化した。その後、尿素の濃度を50mM重炭酸アンモニウム緩衝液で1Mに希釈し、試料をトリプシン(プロテアーゼ/全タンパク質の量の比1/50;w/w)で37℃で一晩インキュベートした。トリプシンの活性を、100μlの溶液当たり1μlの無水のギ酸の添加によりクエンチした。試料を重合成ペプチドの混合物でスパイクし、次いで固相抽出カートリッジ(Sep Pak tC18、50mg、Waters)に脱塩した。その後、溶離液を真空遠心分離機で蒸発乾固させ、次いでLC−PRM分析の前に0.1%ギ酸で再懸濁した。
LC MSのセットアップは、高圧バイナリグラジエント用に構成され、カラム切り替えモードで動作するDionex Ultimate3000RSLCクロマトグラフィシステムからなる。移動相Aは、水中の0.1%ギ酸からなり、相Bはアセトニトリル中の0.1%ギ酸に存し、装填相は水中の0.05%トリフルオロ酢酸及び1%アセトニトリルに存した。250ngの消化された各々の試料に相当するものを注入し、5μl/分でトラップカラム(75μm×2cm、C18 PepMap100、3μm)に装填し、分析カラム(75μm×15cm、C18 PepMap100、2μm)に、300nl/分で、48分間で2%A〜35%Bで開始する線形勾配でさらに溶出した。MSの分析は、PRMモードで操作されるハイブリッド四重極オービトラップ質量分析計(Q Exactive plus、Thermo Scientific)により行った。MSサイクルは、70,000の分解能(200m/z)で実行される完全MS1スキャンで開始され、20の標準化された衝突エネルギーで、35,000の分解能(200m/z)で獲得される、時間スケジュール化した標的化PRMスキャンが続いた。PRM事象の四重極単離ウィンドウを1m/z単位に設定し、内因性ペプチド及び同位体標識ペプチドのそれぞれの対に関するスケジュールされた時間ウィンドウの持続時間を2分に設定した。
全ての分析は、SPSSバージョン20.0(IBM、USA)及びGraph Pad Prism v.6.0(GraphPad Software、CA、米国)で行った。平均化された軽度/重度の面積比を複製の間で計算した。ピアソン相関係数を用いて、同じタンパク質のシグナチャのペプチド間の線形相関を計算した。Kolmogorov−Smirnova検定及びShapiro−Wilk検定によって評価された非正規分布のデータセットに起因して、腫瘍と対照試料との間のモニタされたペプチドの発現の比較を、ノンパラメトリックなMann−Whitney U検定によって評価した。3を超える倍率変化を伴う0.05を下回るP値が、統計的に有意であると考えられた。受信者動作特性(ROC)曲線を用いて、EC対非EC対照群の感度と特異度との間の関係を計算し、それによって各バイオマーカー候補の診断能力を評価した。
20人のEC患者と18人の非EC対照との間の各バイオマーカー候補の発現を比較した。重要なことに、患者と対照の両方共、異常な膣の出血を患っている閉経後女性であり、ECに罹患している患者の93%がこれらの臨床的特徴を示していたが、その15%のみが最終的にECと診断されることになる。
Claims (12)
- 女性生殖器から得られる子宮吸引液試料中のMMP9の発現レベルを判定することを含む、子宮内膜がんの診断又は予後判定の方法。
- 以下のタンパク質:KPYM、ENOA、PRDX1、MIF、GSTP1、CAPG、CADH1、HSPB1、PDIA1、LDHA、CLIC1、CASP3、FABP5、TPIS、LDHA、CTNB1、CH10、NAMPT、及びANXA2の1以上の発現レベルを判定することを更に含む、請求項1に記載の方法。
- KPYM、ENOA、PRDX1、MIF、GSTP1、CAPG、CADH1、HSPB1、PDIA1、LDHA、CLIC1、CASP3、FABP5、TPIS、LDHA、CTNB1、CH10、NAMPT、及びANXA2からなる群から選択される1つのタンパク質の発現レベルを判定することを更に含む、請求項1又は2に記載の方法。
- 前記発現レベルがタンパク質のレベルで判定される、請求項1〜3のいずれか1項に記載の方法。
- タンパク質の前記発現レベルが、前記タンパク質に結合することができる抗体又はその断片を用いて判定される、請求項4に記載の方法。
- 前記抗体又はその断片oがキットの一部を形成する、請求項5に記載の方法。
- 単離された前記試料が子宮体液である、請求項1〜6のいずれか1項に記載の方法。
- 女性生殖器から得られる子宮吸引液試料において、子宮内膜がんを診断又は予後判定するための、インビトロマーカーとしてのMMP9の使用。
- 請求項1〜7のいずれか1項に記載の方法において子宮内膜がんを診断又は予後判定するための、MMP9の使用。
- 固体支持体と、KPYM、ENOA、PRDX1、MIF、GSTP1、CAPG、CADH1、HSPB1、PDIA1、LDHA、CLIC1、CASP3、FABP5、TPIS、LDHA、CTNB1、CH10、NAMPT、及びANXA2からなる群から選択される1以上のタンパク質並びにMMP9の発現レベルを検出するための手段と、を含む、キット。
- KPYM、ENOA、PRDX1、MIF、GSTP1、CAPG、CADH1、HSPB1、PDIA1、LDHA、CLIC1、CASP3、FABP5、TPIS、LDHA、CTNB1、CH10、NAMPT、及びANXA2からなる群から選択される1つのタンパク質並びにMMP9の前記発現レベルを判定するための手段を更に含む、請求項10に記載のキット。
- 前記タンパク質の前記発現レベルを検出するための手段が抗体又はその断片である、請求項10〜11のいずれかに記載のキット。
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KR20230043331A (ko) * | 2021-09-24 | 2023-03-31 | 가천대학교 산학협력단 | C-peptide를 처리한 자궁내막 기질세포의 이동성 변화 기작을 이용한 자궁내막 관련질환의 진단 방법 및 자궁내막 관련질환 치료제의 스크리닝 방법 |
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AU2022315559A1 (en) | 2021-07-23 | 2024-02-15 | Fundació Hospital Universitari Vall D'hebron - Institut De Recerca | Biomarkers for endometrial cancer |
CN113493838B (zh) * | 2021-09-06 | 2021-11-23 | 北京泱深生物信息技术有限公司 | 子宫内膜癌相关的标志分子及其在诊断子宫内膜癌中的应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007202556A (ja) * | 1997-03-20 | 2007-08-16 | Diagnotech Pty Ltd | 子宮内膜ガンの検出 |
US20080090258A1 (en) * | 2006-06-28 | 2008-04-17 | University Of Pittsburgh -Of The Commonwealth System Of Higher Education | Method and composition for diagnosing endometrial cancer |
JP2013500001A (ja) * | 2009-07-24 | 2013-01-07 | ジアディック・バイオテック・アグルパシオン・デ・インテレス・エコノミコ | 子宮内膜がんのマーカー |
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2023
- 2023-01-13 JP JP2023003700A patent/JP7492287B2/ja active Active
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007202556A (ja) * | 1997-03-20 | 2007-08-16 | Diagnotech Pty Ltd | 子宮内膜ガンの検出 |
US20080090258A1 (en) * | 2006-06-28 | 2008-04-17 | University Of Pittsburgh -Of The Commonwealth System Of Higher Education | Method and composition for diagnosing endometrial cancer |
JP2013500001A (ja) * | 2009-07-24 | 2013-01-07 | ジアディック・バイオテック・アグルパシオン・デ・インテレス・エコノミコ | 子宮内膜がんのマーカー |
Non-Patent Citations (2)
Title |
---|
ALEX LOPATA; FRANCA AGRESTA ET AL.: "DETECTION OF ENDOMETRIAL CANCER BY DETERMINATION OF MATRIX METALLOPROTEINASES IN THE UTERINE CAVITY", GYNECOLOGIC ONCOLOGY, vol. VOL:90, NR:2, JPN5019003683, August 2003 (2003-08-01), GB, pages 318 - 324, ISSN: 0004958318 * |
ELENA MARTINEZ-GARCIA ET AL.: "DEVELOPMENT OF A SEQUENTIAL WORKFLOW BASED ON LC-PRM FOR THE VERIFICATION OF ENDOMETRIAL CANCER PROT", ONCOTARGET, vol. VOL:7, NR:33, JPN5019003685, 16 July 2016 (2016-07-16), pages 53102 - 53115, XP055369199, ISSN: 0004958319, DOI: 10.18632/oncotarget.10632 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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KR20230043331A (ko) * | 2021-09-24 | 2023-03-31 | 가천대학교 산학협력단 | C-peptide를 처리한 자궁내막 기질세포의 이동성 변화 기작을 이용한 자궁내막 관련질환의 진단 방법 및 자궁내막 관련질환 치료제의 스크리닝 방법 |
KR102640230B1 (ko) | 2021-09-24 | 2024-02-22 | 가천대학교 산학협력단 | C-peptide를 처리한 자궁내막 기질세포의 이동성 변화 기작을 이용한 자궁내막 관련질환의 진단 방법 및 자궁내막 관련질환 치료제의 스크리닝 방법 |
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