Anti-CDC25B autoantibody predicts poor prognosis in patients with advanced esophageal squamous cell carcinoma.

Anti-CDC25B autoantibody predicts poor prognosis in patients with advanced esophageal squamous cell carcinoma.
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抗CDC25B自身抗体预测晚期食管鳞状细胞癌患者预后不良

DOI:
10.1186/1479-5876-8-81
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发表时间:
2010-09-03
影响因子:
7.4
通讯作者:
Liu WL
Liu WL
中科院分区:
医学2区
文献类型:
--
作者:
Dong J;Zeng BH;Xu LH;Wang JY;Li MZ;Zeng MS;Liu WL

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背景癌基因CDC25B磷酸酶在癌细胞生长中发挥重要作用。我们最近报道,食管鳞状细胞癌 (ESCC) 患者的 CDC25B 自身抗体 (CDC25B-Abs) 血清水平显着高于健康个体和其他类型癌症患者;然而,CDC25B-Ab 的潜在诊断或预后意义尚不清楚。本研究的目的是评估 ESCC 患者血清 CDC25B-Ab 的临床意义。方法使用反向捕获酶联免疫吸附测定 (ELISA) 测量 134 名原发性 ESCC 患者和 134 名健康对照者的血清中的 CDC25B 自身抗体,其中抗 CDC25B 抗体结合从 Eca-109 ESCC 肿瘤细胞纯化的 CDC25B 抗原。将CDC25B血清自身抗体的临床病理意义与肿瘤标志物癌胚抗原(CEA)、鳞状细胞癌抗原(SCC-Ag)和细胞角蛋白19片段抗原21-1(CYFRA21-1)进行比较。结果ESCC患者血清中存在较高水平的CDC25B自身抗体(A450 = 0.917,SD = 0.473)高于健康对照受试者的血清(A450 = 0.378,SD = 0.262,P < 0.001)。 CDC25B-Ab 的受试者工作特征 (ROC) 曲线下面积为 0.870 (95% CI: 0.835-0.920)。当CDC25-Abs阳性样本被定义为A450大于截止值0.725的样本时,CDC25B-Abs检测ESCC的敏感性和特异性分别为56.7%和91.0%。肿瘤标志物 CEA、SCC-Ag 和 CYFRA21-1 检测呈阳性的患者相对较少(分别为 13.4%、17.2% 和 32.1%)。 CEA、SCC、CYFRA21-1 和 CDC25B-Ab 组合检测呈阳性的 ESCC 患者数量 (64.2%) 明显高于 CEA、SCC-Ag 和 CYFRA21-1 组合检测呈阳性的人数 (41.0%,P< 0.001)。血清中CDC25B自身抗体浓度与肿瘤分期显着相关(P<0.001)。尽管对整个患者库的检查显示CDC25B自身抗体与总生存率之间没有明显关系,但在III-IV期肿瘤患者亚组中,CDC25B血清阳性患者的累积五年生存率为6.7%,而CDC25B血清阴性患者的累积五年生存率为43.4%(P = 0.001,对数秩)。 N1亚组中,CDC25B血清阳性患者的累积五年生存率为13.6%,CDC25B血清阴性患者的累积五年生存率为54.5%(P=0.040,log-rank)。结论血清CDC25B-Abs检测优于肿瘤标志物CEA、SCC-Ag和CYFRA21-1检测对ESCC的诊断,且CDC25B-Ab 是晚期 ESCC 的潜在预后血清学标志物。
BackgroundThe oncogene CDC25B phosphatase plays an important role in cancer cell growth. We have recently reported that patients with esophageal squamous cell carcinoma (ESCC) have significantly higher serum levels of CDC25B autoantibodies (CDC25B-Abs) than both healthy individuals and patients with other types of cancer; however, the potential diagnostic or prognostic significance of CDC25B-Abs is not clear. The aim of this study is to evaluate the clinical significance of serum CDC25B-Abs in patients with ESCC.MethodsCDC25B autoantibodies were measured in sera from both 134 patients with primary ESCC and 134 healthy controls using a reverse capture enzyme-linked immunosorbent assay (ELISA) in which anti-CDC25B antibodies bound CDC25B antigen purified from Eca-109 ESCC tumor cells. The clinicopathologic significance of CDC25B serum autoantibodies was compared to that of the tumor markers carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragment antigen 21-1(CYFRA21-1).ResultsHigher levels of CDC25B autoantibodies were present in sera from patients with ESCC (A450= 0.917, SD = 0.473) than in sera from healthy control subjects (A450= 0.378, SD = 0.262,P< 0.001). The area under the receiver operating characteristic (ROC) curve for CDC25B-Abs was 0.870 (95% CI: 0.835-0.920). The sensitivity and specificity of CDC25B-Abs for detection of ESCC were 56.7% and 91.0%, respectively, when CDC25-Abs-positive samples were defined as those with an A450greater than the cut-off value of 0.725. Relatively few patients tested positive for the tumor markers CEA, SCC-Ag and CYFRA21-1 (13.4%, 17.2%, and 32.1%, respectively). A significantly higher number of patients with ESCC tested positive for a combination of CEA, SCC, CYFRA21-1 and CDC25B-Abs (64.2%) than for a combination of CEA, SCC-Ag and CYFRA21-1 (41.0%,P< 0.001). The concentration of CDC25B autoantibodies in serum was significantly correlated with tumor stage (P< 0.001). Although examination of the total patient pool showed no obvious relationship between CDC25B autoantibodies and overall survival, in the subgroup of patients with stage III-IV tumors, the cumulative five-year survival rate of CDC25B-seropositive patients was 6.7%, while that of CDC25B-seronegative patients was 43.4% (P= 0.001, log-rank). In the N1 subgroup, the cumulative five-year survival rate of CDC25B-seropositive patients was 13.6%, while that of CDC25B-seronegative patients was 54.5% (P= 0.040, log-rank).ConclusionsDetection of serum CDC25B-Abs is superior to detection of the tumor markers CEA, SCC-Ag and CYFRA21-1 for diagnosis of ESCC, and CDC25B-Abs are a potential prognostic serological marker for advanced ESCC.
DOI: 10.1038/nprot.2006.66
发表时间: 2006-01-01
期刊: NATURE PROTOCOLS
影响因子: 14.8
作者:
Ehrlich, Joshua R.;Qin, Shuzhen;Liu, Brian C-S
通讯作者: Liu, Brian C-S
DOI: 10.1054/bjoc.2001.1934
发表时间: 2001-08-03
影响因子: 8.8
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DOI: 10.1378/chest.116.suppl_3.463s
发表时间: 1999-12-01
期刊: CHEST
影响因子: 9.6
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发表时间: 2008-06-01
影响因子: 3.8
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通讯作者: Taylor, Philip R.
DOI: 10.1016/j.canlet.2005.06.040
发表时间: 2005-11-18
期刊: CANCER LETTERS
影响因子: 9.7
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