New Dual Monoclonal ELISA for Measuring Plasma Osteopontin as a Biomarker Associated with Survival in Prostate Cancer: Clinical Validation and Comparison of Multiple ELISAs

New Dual Monoclonal ELISA for Measuring Plasma Osteopontin as a Biomarker Associated with Survival in Prostate Cancer: Clinical Validation and Comparison of Multiple ELISAs
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DOI:
10.1373/clinchem.2008.117465
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发表时间:
2009-05-01
期刊:
影响因子:
9.3
通讯作者:
Chambers, Ann F.
Chambers, Ann F.
中科院分区:
医学1区
文献类型:
--
作者:
Anborgh, Pieter H.;Wilson, Sylvia M.;Chambers, Ann F.

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背景技术背景:先前开发的检测骨桥蛋白(OPN)血浆浓度的单克隆/多克隆ELISA(Mono/Poly)显示可提供乳腺癌、前列腺癌和其他癌症的预后信息。在这里,我们描述了一种新的双单克隆(双单)检测的临床验证。我们将两种检测方法与识别OPN蛋白确定区域的4种检测方法(双多克隆系统5-1、4-1、4-3和多克隆-单克隆系统1-3)进行比较。使用6 ELISA,我们测量OPN在血浆中从66例去势抵抗性前列腺癌,我们评估了每一个分析的能力,以预测患者survival.RESULTS:测定不同的血浆OPN浓度,中位数值范围从112到1740 μ g/L,并能够预测患者的生存。通过OPN三分位数生存期的考克斯单变量回归,单/多和双单ELISA具有最高的对数秩卡方检验值。在我们的样本中,调整了与生存独立相关的风险因素后,OPN仅在Mono/Poly和Dual Mono system.CONCLUSIONS:OPN血浆值根据所用的测定方法显著变化。在去势抵抗性前列腺癌男性人群中,只有Mono/Poly和Dual Mono系统与生存率独立相关。临床验证的双单克隆ELISA的可用性将为癌症和其他病理学中OPN血浆浓度的研究提供一致的试剂。(C)2009年美国临床化学协会
BACKGROUND: A previously developed monoclonal/polyclonal ELISA (Mono/Poly) to detect plasma concentrations of osteopontin (OPN) was shown to provide prognostic information in breast, prostate, and other cancers. Here we describe the clinical validation of a new dual monoclonal (Dual Mono) assay. We compared both assays with 4 assays that recognize defined regions of OPN protein (dual polyclonal systems 5-1, 4-1, 4-3 and polyclonal-monoclonal system 1-3).METHODS: OPN sequences recognized by the monoclonal antibodies that make up the Dual Mono ELISA were identified by Pepscan CLIPS (TM) analysis. Using the 6 ELISAs, we measured OPN in plasma from 66 patients with castration-resistant prostate cancer, and we assessed the ability of each assay to predict patient survival.RESULTS: The assays varied in measured plasma OPN concentrations, with median values ranging from 112 to 1740 mu g/L, and ability to predict patient survival. By Cox univariable regression of survival by tertiles of OPN, the Mono/Poly and Dual Mono ELISAs had the highest log-rank chi(2) values. After adjustment for risk factors independently associated with Survival in our samples, OPN remained associated with Survival only for the Mono/Poly and Dual Mono systems.CONCLUSIONS: OPN plasma values varied significantly depending oil the assay used. Only the Mono/Poly and Dual Mono systems were independently associated with survival in a population of men with castration-resistant prostate cancer. The availability of a clinically validated, dual monoclonal-based ELISA will provide consistent reagents for studies of OPN plasma concentrations in cancer and other pathologies. (C) 2009 American Association for Clinical Chemistry