前立腺癌骨転移マーカーとしての尿中Cross-linked N-telopeptides of type 1 collagenの有用性 ―PICP, PINP, ICTPとの比較―

Abstract

近年血液中のI型コラーゲンの代謝産物であるPICP, PINPが骨形成マーカー, ICTPが骨吸収マーカーとして, 骨代謝や骨転移病巣の評価や骨転移の補助療法に用いられつつある.最近, 尿中type I collagen cross-linked N-telopeptides(NTx)の測定が可能となり, 他の骨代謝マーカー同様に利用可能であればその有用性は高い.そこで前立腺癌患者を治療前・再燃時で骨転移あり15例(1群), 内分泌療法有効で骨転移ありの11症例(2群), 限局性前立腺癌で骨転移なしの11症例(3群)に分け, 尿中NTxと血中PICP, PINP, ICTPを同時測定して比較検討した.その結果, PICP・PINP・ICTPの血中濃度および尿中NTxはいずれも1群と2群, 1群と3群間で有意差を認めた.NTxとPICP, PINP, ICTPそれぞれとの相関係数は0.834, 0.610, 0.467であった.以上の結果からNTxを骨転移有無の診断に利用することは困難であるが, ホルモン療法の治療効果判定, 骨転移の補助診断には採血を必要としない点で有用と考えられた

Type I collagen cross-linked N-telopeptide (NTx) in urine, the degraded form of type I collagen cross-linked in bone, has been evaluated as a marker of bone resorption. In this study, the clinical usefulness of NTx as a marker of bone metastasis of prostate cancer was compared with that the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type I procollagen (PINP), and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in serum. We assessed 37 cases of prostatic cancer in which the diagnosis had been confirmed pathologically. The patients were 15 patients with prostatic cancer with bone metastasis (before treatment or during a relapse) (Group 1); 11 patients, with bone metastasis, but for whom treatment was effective and condition had stabilized (Group 2); and 11 patients, with localized prostatic cancer and no evidence of bone metastasis (Group 3). The serum PICP, PINP, and ICTP levels and concentration of NTx in urine were compared among the three groups with the Mann-Whitney U test, with p values less than 0.05 considered significant. Urine NTx concentrations in Groups 1, 2 and 3 were 539.3 +/- 202.9, 160.6 +/- 97.6 and 48.6 +/- 7.6 nMBCE/mMCr, respectively. The differences between the Group 1 and Group 2 and between Group 1 and Group 3 were significant (p < 0.01 and p < 0.001). The differences between Group 1 and Group 3 and between Group 2 and Group 3 were significant for serum PICP, PINP and ICTP concentrations (p < 0.05). The correlation coefficient between urine NTx and each serum bone metabolic marker was 0.8 for PICP, 0.4 for PINP and 0.5 for ICTP. These bone metabolic markers are promising clinical markers of bone metastatic and may be useful for prediction of therapeutic efficacy and recurrence in bone and quantification of the extent of bone metastates.