Tumor type M2 pyruvate kinase (TuM2-PK) as a novel plasma tumor marker in melanoma
Tumor type M2 pyruvate kinase (TuM2-PK) as a novel plasma tumor marker in melanoma
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DOI：
10.1002/ijc.21073
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发表时间：
2005-12-10
影响因子：
6.4
通讯作者：
Schadendorf, D
中科院分区：
文献类型：
--
作者：
Ugurel, S;Bell, N;Schadendorf, D
增殖细胞表达丙酮酸激酶同工酶M2 （M2- pk）。这种酶以活性四聚体和非活性二聚体的形式存在。二聚体形式主要存在于肿瘤细胞中，因此被称为肿瘤M2-PK （TuM2-PK）。TuM2-PK分子被释放到外周血中，因此可能作为癌症患者肿瘤负荷的标记物。我们的研究旨在研究TuM2-PK作为黑色素瘤患者的潜在血浆标志物，与已建立的血清标志物S100 β相比。我们分别用夹心ELISA和免疫荧光测定法测定了300例黑色素瘤患者和53例健康对照者的血浆中TuM2-PK和相应血清样本中S100 β的浓度。与健康对照组相比，黑色素瘤患者血浆TuM2-PK浓度显著升高（9.30 U/ml vs. 7.20 U/ml, p = 0.0036），并与肿瘤负荷（p < 0.0005）和疾病分期（p < 0.0005）相关。血浆TuM2-PK升高（截止值= 15 U/ml）的患者总体生存率（p < 0.000005）和无进展生存率（p = 0.023）降低。多因素分析显示，血浆TuM2-PK和血清S100 β是转移患者总生存的独立预测因子。血浆TuM2-PK和血清S100 β均未显示无肿瘤患者的预后相关性。虽然与血浆TuM2-PK相比，血清S100 β预测疾病进展或死亡的敏感性和特异性更高，但与单独使用血清S100 β相比，这两种标志物的联合使用改善了对预后的估计。(c) 2005 Wiley-Liss。公司。
Proliferating cells express the pyruvate kinase isoenzyme type M2 (M2-PK). This enzyme exists as an active tetramer and an inactive dimer. The dimeric form is predominantly found in tumor cells and is therefore termed Tumor M2-PK (TuM2-PK). TuM2-PK molecules are released into the peripheral blood and may hereby function as a marker of tumor load in cancer patients. Our study was aimed to investigate TuM2-PK as a potential plasma marker in melanoma patients compared to the well-established serum marker S100 beta. We measured the concentration of TuM2-PK in plasma and S100 beta in corresponding serum samples from 300 melanoma patients and 53 healthy controls using a sandwich ELISA and an immunoluminometric assay, respectively. Plasma concentrations of TuM2-PK were significantly increased in melanoma patients compared to healthy controls (9.30 U/ml vs. 7.20 U/ml; p = 0.0036) and correlated with tumor load (p < 0.0005) and disease stage (p < 0.0005). Patients with elevated plasma TuM2-PK (cut-off = 15 U/ml) presented a reduced overall (p < 0.000005) and progression-free (p = 0.023) survival. Multivariate analysis revealed plasma TuM2-PK and serum S100 beta as independent predictors of overall survival in metastasized patients. Neither plasma TuM2-PK nor serum S100 beta showed prognostic relevance for tumor-free patients. Although the sensitivity and specificity to predict disease progression or death was higher for serum S100 beta compared to plasma TuM2-PK, the combination of both markers improved the estimation of prognosis compared to that of serum S100 beta alone. (c) 2005 Wiley-Liss. Inc.