Clinical Significance and Prognostic Value of Serum Dickkopf-1 Concentrations in Patients with Lung Cancer
Clinical Significance and Prognostic Value of Serum Dickkopf-1 Concentrations in Patients with Lung Cancer
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肺癌患者血清Dickkopf-1浓度的临床意义和预后价值
DOI：
10.1373/clinchem.2009.125641
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发表时间：
2009-09-01
影响因子：
9.3
通讯作者：
Qin, Wen Xin
中科院分区：
文献类型：
--
作者：
Sheng, Shi Le;Huang, Gang;Qin, Wen Xin
背景：Dickkopf-1 （DKK1）是一种分泌蛋白，被认为是Wnt信号通路的负调节因子，与几种类型癌症的发展有关。血清DKK1在肺癌中的临床意义尚未确定。方法：建立了一种新的时间分辨免疫荧光测定法。通过这种方法，我们研究了592例恶性肿瘤患者、72例良性肺部疾病患者和120例健康对照者的血清DKK1浓度。测定血清细胞角蛋白19片段和神经元特异性烯醇化酶值。结果：肺癌患者血清DKK1浓度明显高于其他恶性肿瘤或肺部良性疾病患者及健康对照组。胃癌、结直肠癌、卵巢癌和子宫颈腺癌患者血清DKK1浓度与健康对照组相比显著降低。同时应用DKK1和细胞角蛋白19片段增加了敏感性，正确识别出89.6%的非小细胞肺癌患者为阳性。同时使用DKK1和神经元特异性烯醇化酶可将检测小细胞肺癌的灵敏度提高到86.2%。DKK1浓度随分期、肿瘤类别、淋巴结和远处转移的存在而增加，与组织学、患者年龄和性别无关。与DKK1浓度较低的患者相比，DKK1浓度为22.6 μ g/L或更高的患者的生存率有统计学意义上的显著降低。结论：DKK1在肺癌中优先表达。DKK1浓度的升高与肺癌患者的肿瘤进展和生存期的降低显著相关。(C) 2009年美国临床化学学会
BACKGROUND: Dickkopf-1 (DKK1), a secreted protein, is known as a negative regulator of the Wnt signaling pathway, which has been implicated in the development of several types of cancers. Clinical significance of serum DKK1 in lung cancer remains to be determined.METHODS: A novel time-resolved immunofluorometric assay was developed. By use of this method, we investigated the serum concentrations of DKK1 in 592 patients with malignancies, 72 patients with benign lung disease, and 120 healthy controls. Serum cytokeratin 19 fragment and neuron-specific enolase values were obtained.RESULTS: Serum DKK1 concentrations were significantly higher in patients with lung cancer than in patients with other malignant tumors or benign lung diseases and healthy controls. Serum concentrations of DKK1 were decreased significantly in groups of patients with gastric cancer, colorectal cancer, ovarian cancer, and cervical adenocarcinoma compared with healthy controls. Application of both DKK1 and cytokeratin 19 fragment increased sensitivity, correctly identifying 89.6% of the non-small cell lung cancer patients as positive. The use of both DKK1 and neuron-specific enolase increased sensitivity to detect small cell lung cancer to 86.2%. DKK1 concentrations increased with stage, tumor class, and presence of lymph node and distant metastases, regardless of histology and patient age and sex. Patients with a DKK1 concentration of 22.6 mu g/L or higher had a statistically significantly diminished survival compared with patients whose DKK1 values were lower.CONCLUSIONS: DKK1 was preferentially expressed in lung cancer. Increasing concentrations of DKK1 were significantly associated with tumor progression and decreased survival in patients with lung cancer. (C) 2009 American Association for Clinical Chemistry