Development of urinary calreticulin test for the diagnosis of urothelial cancer

用于诊断尿路上皮癌的尿钙网蛋白测试的发展

• 批准号: 19591844
• 负责人: 影山 進
• 金额: $ 2.91万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2008
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19591844/
• 关键词: 尿路上皮癌; 腫瘍マーカー; カルレティキュリン; プロテオミクス

われわれは尿路上皮癌のプロテオーム解析により,小胞体タンパク質カルレティキュリン(CRT)が癌患者尿中で高率に検出されることを示し,尿中診断マーカーとしての可能性を示唆した(Kageyama et al.,Clin Chem,2004).今回,ELISA 法による測定キットを作製したので,その診断能につき報告する.【方法】リコンビナントヒトCRT を大腸菌に発現させ標準物質とした.ビーズに抗CRT モノクローナル抗体を固相化し96 穴プレートに入れ,尿検体と反応後にPOD 標識抗CRT ポリクローナル抗体を結合させ化学発光で検出する,2 抗体サンドイッチELISA 法で測定した. 対象は膀胱癌患者尿(109検体), 非膀胱癌患者尿(60検体, 腎癌, 前立腺癌, 前立腺肥大症, 尿路結石症など), および特に尿路異常を認めない健常者尿(40検体)である. 【結果】全209検体のCRT濃度測定の結果からROC曲線を作成し, もっとも診断効率の良い, 2.85ng/mL 以下を基準値と設定した. 膀胱癌患者尿(109検体)のCRT中央値は12.7ng/mL, 74検体で陽性で感度は67.9%であった. 病理学的因子でみると, 異型度G1:5.5±7.7(mean±SD), G2:42.3±63.8, G3:74.3±149.9, 深達度Tis : 15.6±17.5, Ta : 48.9±130.6, T1 : 56.1±74.4, T2-4:69.0±86.0, 腫瘍長径 < 1cm:16.4±30.6, 1-3cm:60.4±83.4, 3cm<:136.6±225.5ng/mLで, それぞれ臨床的悪性度が進むにつれてCRT値が増加した. 一方, 非膀胱癌患者尿では中央値<0.5ng/mLで, 15検体(25%)で偽陽性を呈した. 健常者尿と併せて非膀胱癌群とらえると, 100検体中20検体で偽陽性を示し, 特異度は80%であった. 【考察】尿中CRTは膀胱癌尿中診断マーカーとして臨床応用可能と考えられた.

The high incidence of urinary tract cancer (CRT) in patients with urothelial carcinoma was demonstrated by the possibility of urinary diagnosis (Kageyama et al., Clin Chem,2004). In this paper,ELISA method for the determination of the detection of the virus, the diagnosis can be reported. [Method] CRTs are developed from Escherichia coli and reference materials. Anti-CRT antibodies were immobilized at 96 sites, and then detected by ELISA. Urine samples from bladder cancer patients (109 samples), urine samples from non-bladder cancer patients (60 samples), kidney cancer, prostate adenocarcinoma, prostate hyperplasia, urolithiasis), and urine samples from healthy individuals (40 samples). [Results] The ROC curve of CRT concentration measurement results of all 209 samples was established, and the diagnostic efficiency was good. The reference value was set below 2.85 ng/mL. The CRT central value of urine (109 samples) in bladder cancer patients was 12.7 ng/mL, and the sensitivity of 74 samples was 67.9%. Pathological factors were: G1:5.5±7.7(mean±SD), G2:42.3±63.8, G3:74.3±149.9, Tis : 15.6±17.5, Ta : 48.9±130.6, T1 : 56.1±74.4, T2-4:69.0±86.0, tumor length < 1cm:16.4±30.6, 1-3cm:60.4±83.4, 3cm<136.6±225.5ng/mL, which indicated that the clinical severity of the lesion increased. In one case, urine samples from non-bladder cancer patients were found to be false-positive (25%) when urine samples were <0.5 ng/mL. In healthy individuals, 20 out of 100 samples showed false positive, and the specificity was 80%. [Investigation] Urinary CRT bladder cancer urinary diagnosis

项目成果

Urinary calreticulin in the diagnosis of urinary bladder urothelial carcinoma

尿钙网蛋白在膀胱尿路上皮癌诊断中的应用

• 发表时间: 2009
• 期刊: International Journal of Urology 16
• 作者: Kageyama S;Isono T;Matsuda S;Ushio Y;Satomura S;Terai A;Arai Y;Kawakita M;Okada Y;Yoshiki T
• 通讯作者: Yoshiki T