肺癌(lung cancer)是當前世界各地最常見的惡性腫瘤之一,是一種嚴重威脅人民健康和生命的疾病。每年全球新增肺癌病例120萬,，每30秒就有人因此死亡,。我國肺癌的發(fā)病率和死亡率高居腫瘤第一位，80%患者在確診1年內(nèi)死亡,。
上海交通大學醫(yī)學院附屬仁濟醫(yī)院黃鋼教授和上海市腫瘤研究所覃文新教授經(jīng)過多年合作研究,，在腫瘤標志物研究領域取得重要進展，發(fā)現(xiàn)肺癌血清學標志物DKK1,，相關文章“Clinical Significance and Prognostic Value of Serum Dickkopf-1 Concentrations in Patients with Lung Cancer” 近日由課題組成員仁濟醫(yī)院核醫(yī)學科盛世樂醫(yī)師作為第一作者發(fā)表于臨床檢驗醫(yī)學權威科學雜志Clinical Chemistry,。
盡管目前各種診斷技術日新月異，但仍有50%~70%肺癌患者被確診時已為晚期,，喪失了手術和放化療治療機會,。有研究表明，早期肺癌患者綜合治療后,，5年生存率可達60%～90%,。提高肺癌患者生存率的關鍵在于早發(fā)現(xiàn)、早診斷,、早治療,，因此，尋找好的血清腫瘤標志物成為研究熱點,。但由于肺癌組織病理的多樣性,、同種病理腫瘤細胞的異質(zhì)性和腫瘤生物學行為的復雜性，目前還未找到一種敏感度和特異度均很高的肺癌血清學標志物,。
課題組研究發(fā)現(xiàn),，與其它惡性腫瘤、良性肺疾病和健康對照組相比,，肺癌患者血清DKK1濃度明顯升高,；聯(lián)合檢測血清DKK1和CYFRA21-1可將非小細胞型肺癌的診斷靈敏度提高至89.6%，血清DKK1和NSE聯(lián)合檢測可將小細胞型肺癌的診斷靈敏度提高至86.2% ,；血清DKK1水平還與肺癌的臨床分期,、分級,、有無淋巴結(jié)和遠處轉(zhuǎn)移、生存期等相關,。這一發(fā)現(xiàn)將為肺癌的診斷和治療提供新思路,。
課題組還首次在國內(nèi)外采用超靈敏時間分辨熒光免疫分析技術，建立了DKK1檢測方法,，為血清DKK1檢測提供了準確,、靈敏、高效的技術平臺,，并為該項目用于臨床奠定了基礎,，同時課題組已申請了兩項DKK1在癌癥診斷和檢測方面的專利，擁有完全自主知識產(chǎn)權,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
