肺癌(lung cancer)是当前世界各地最常见的恶性肿瘤之一,是一种严重威胁人民健康和生命的疾病。每年全球新增肺癌病例120万，每30秒就有人因此死亡。我国肺癌的发病率和死亡率高居肿瘤第一位，80%患者在确诊1年内死亡。
上海交通大学医学院附属仁济医院黄钢教授和上海市肿瘤研究所覃文新教授经过多年合作研究，在肿瘤标志物研究领域取得重要进展，发现肺癌血清学标志物DKK1，相关文章“Clinical Significance and Prognostic Value of Serum Dickkopf-1 Concentrations in Patients with Lung Cancer” 近日由课题组成员仁济医院核医学科盛世乐医师作为第一作者发表于临床检验医学权威科学杂志Clinical Chemistry。
尽管目前各种诊断技术日新月异，但仍有50%~70%肺癌患者被确诊时已为晚期，丧失了手术和放化疗治疗机会。有研究表明，早期肺癌患者综合治疗后，5年生存率可达60%～90%。提高肺癌患者生存率的关键在于早发现、早诊断、早治疗，因此，寻找好的血清肿瘤标志物成为研究热点。但由于肺癌组织病理的多样性、同种病理肿瘤细胞的异质性和肿瘤生物学行为的复杂性，目前还未找到一种敏感度和特异度均很高的肺癌血清学标志物。
课题组研究发现，与其它恶性肿瘤、良性肺疾病和健康对照组相比，肺癌患者血清DKK1浓度明显升高；联合检测血清DKK1和CYFRA21-1可将非小细胞型肺癌的诊断灵敏度提高至89.6%，血清DKK1和NSE联合检测可将小细胞型肺癌的诊断灵敏度提高至86.2% ；血清DKK1水平还与肺癌的临床分期、分级、有无淋巴结和远处转移、生存期等相关。这一发现将为肺癌的诊断和治疗提供新思路。
课题组还首次在国内外采用超灵敏时间分辨荧光免疫分析技术，建立了DKK1检测方法，为血清DKK1检测提供了准确、灵敏、高效的技术平台，并为该项目用于临床奠定了基础，同时课题组已申请了两项DKK1在癌症诊断和检测方面的专利，拥有完全自主知识产权。（生物谷Bioon.com）
生物谷推荐原始出处：
Clinical Chemistry July 23, 2009; 10.1373/clinchem.2009.125641
Clinical Significance and Prognostic Value of Serum Dickkopf-1 Concentrations in Patients with Lung Cancer
Shi Le Sheng1,2, Gang Huang1,2,a, Bin Yu3 and Wen Xin Qin3,a
1 Department of Nuclear Medicine, Renji hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;2 Institute of Health Sciences, SIBS, CAS and SJTUSM, Shanghai, China;3 National Laboratory for Oncogenes and Related Genes, WHO Collaborating Center for Research on Cancer, Shanghai Cancer Institute, Shanghai Jiao Tong University Medical School, Shanghai, China.
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 μg/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 DKK1were significantly associated with tumor progression and decreased survival in patients with lung cancer.
