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尿激酶型纤溶酶原激活物受体游离结构域I在肺鳞状细胞癌组织中的预后影响

Prognostic impact of liberated domain I of the urokinase plasminogen activator receptor in squamous cell lung cancer tissue.

作者信息

Almasi Charlotte Elberling, Høyer-Hansen Gunilla, Christensen Ib Jarle, Danø Keld, Pappot Helle

机构信息

The Finsen Laboratory, Rigshospitalet, Strandboulevarden 49, Copenhagen DK-2100, Denmark.

出版信息

Lung Cancer. 2005 Jun;48(3):349-55. doi: 10.1016/j.lungcan.2004.11.020.

Abstract

OBJECTIVES

The purpose of this study was to determine the prognostic impact of liberated domain I of the urokinase plasminogen activator receptor, uPAR(I), in tumour extracts from patients resected for the squamous cell carcinoma (SCC) of the lung.

MATERIALS AND METHODS

A recently developed time-resolved fluoroimmunoassay for uPAR(I), TR-FIA 3, was validated using a pool of SCC tumour extracts. This assay was then used to measure the levels of uPAR(I) in tumour extracts from 63 SCC patients. Overall survival of the patients was measured from the day of surgical resection until death or until a review after a median of 144 months observation. The Cox proportional hazard model was used for uni- and multivariate survival analysis.

RESULTS

TR-FIA 3 was found to measure uPAR(I) in SCC tumour extracts with high precision, accuracy and specificity. Univariate analysis using log transformed uPAR(I) concentrations showed that there was an increasing risk of mortality with increasing uPAR(I) levels in SCC tumour extracts, the hazard ratio (HR) being 2.9 with a P-value of 0.003. In a multivariate analysis, including uPAR(I), gender, age, nodal status, tumour size and levels of uPAR immunoreactivity measured by ELISA, statistically significant prognostic impact was found only for levels of uPAR(I) (HR 3.7, P=0.002) and tumour size (HR 2.4, P=0.02).

CONCLUSION

uPAR(I) levels in the extracts of primary tumours independently predicted overall survival of 63 patients with SCC.

摘要

目的

本研究旨在确定尿激酶型纤溶酶原激活物受体游离结构域I(uPAR(I))对接受肺鳞状细胞癌(SCC)切除术患者肿瘤提取物的预后影响。

材料与方法

使用一组SCC肿瘤提取物对最近开发的uPAR(I)时间分辨荧光免疫分析法(TR-FIA 3)进行验证。然后用该分析法测量63例SCC患者肿瘤提取物中uPAR(I)的水平。从手术切除之日起测量患者的总生存期,直至死亡或在中位观察144个月后进行复查。采用Cox比例风险模型进行单因素和多因素生存分析。

结果

发现TR-FIA 3能够高精度、准确且特异的测量SCC肿瘤提取物中的uPAR(I)。使用对数转换后的uPAR(I)浓度进行单因素分析显示,SCC肿瘤提取物中uPAR(I)水平升高,死亡风险增加,风险比(HR)为2.9,P值为0.003。在多因素分析中,纳入uPAR(I)、性别、年龄、淋巴结状态、肿瘤大小以及通过酶联免疫吸附测定法测量的uPAR免疫反应性水平,结果发现只有uPAR(I)水平(HR 3.7,P = 0.002)和肿瘤大小(HR 2.4,P = 0.02)具有统计学显著的预后影响。

结论

原发性肿瘤提取物中的uPAR(I)水平可独立预测63例SCC患者的总生存期。

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