Detection of early stage cancers and assessment of proliferative potensitals of cancers through measurement of urinary diacetylsperime

各种<12>肿瘤性疾病患者尿液中N ^1，N ^ -二乙酰精胺（DiAcSpm）的排泄增加。我们开发了一种ELISA系统，使用针对DiAcSpm的高度特异性抗体轻松测定尿液DiAcSpm水平，并分析了许多癌症患者尿液中的DiAcSpm。尿DiAcSpm对结肠癌诊断的敏感性为75.8%（0.25μmol/g肌酐，平均值± 2S.D.）。以52例健康对照者为界值，显著高于血清CEA（39.5%）和CA 19 -9（14.1%）。83例乳腺癌患者尿DiAcSpm的敏感性（60.2%）高于CEA（37.3%）和CA 15 -3（37.3%）。我们进一步证明，DiAcSpm在60%的早期临床分期（即0期和I期）的结直肠癌患者中升高至临界值以上。术前DiAcSpm低于临界值的患者（占总患者的25%）很少在术后1.5年内死于癌症，约占总患者的10%。DiAcSpm值高于临界值3倍的患者的预后显著差于DiAcSpm值较低的患者。提示术前DiAcSpm值与患者的预后密切相关。在成功治疗包括前列腺癌、结肠癌和脑肿瘤的癌症患者后，DiAcSpm恢复至正常水平，而在明显有效治疗后，DiAcSpm水平仍远高于正常限度时，预后不良。因此，尿DiAcSpm可能被认为是一种新的高效肿瘤标记物，可用于肿瘤诊断、判断治疗效果和预测患者预后。

Excretion of N^1,N^<12>-diacetylspermine (DiAcSpm) in the urine is increased in patients with various neoplastic diseases. We developed an ELISA system for easy determination of urinary DiAcSpm level using a highly specific antibody against DiAcSpm, and analyzed DiAcSpm in the urine of a number of cancer patients. The sensitivity of urinary DiAcSpm for colon cancer patients was 75.8% (with 0.25μmol/g creatinine, that represents mean + 2S.D. for 52 healthy controls, as a cut-off value), which was markedly higher than that of serum CEA (39.5%), and CA19-9 (14.1%). The sensitivity of urinary DiAcSpm for 83 breast cancer patients (60.2%) was higher than that of CEA (37.3%) and CA15-3 (37.3%). We further demonstrated that DiAcSpm was elevated above the cut-off value in 60% of colorectal cancer patients at earlier clinical stages, namely stage 0 and stage I. Patients whose DiAcSpm was lower than the cut-off value before surgery (25% of the total patients) rarely died of cancer within 1.5 year period after surgery, during which about 10% of the total patients died. Prognosis of patients whose DiAcSpm value was higher than 3 times the cut-off value was significantly poorer than patients with lower DiAcSpm value. This indicate that DiAcSpm value before operation is well correlated with the prognosis of a patient. DiAcSpm recovered to a normal level after a successful treatment of cancer patients including prostate cancer, colon cancer and brain tumor, while the prognosis was poor when DiAcSpm level remained far above the normal limit after apparently effective treatment. Urinary DiAcSpm may thus be considered a novel high performance tumor marker useful in tumor diagnosis, in judging the effectiveness of a treatment and in foreseeing prognosis of patients.