Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA.
Clin Chim Acta. 2012 Oct 9;413(19-20):1506-11. doi: 10.1016/j.cca.2012.06.017. Epub 2012 Jun 18.
Assays used for discovery of biomarkers should be robust and high-throughput, capable of analyzing a sufficiently large number of samples over a sufficiently long period of time with good precision.
We evaluated the analytical performance of the Bio-Plex Pro™ Human Cancer Biomarker Panel 1, a 16-plex multiplex immunoassay, in serum for composite profiling of angiogenic factors. Because prostate cancer progression and metastasis are pathological events closely linked to angiogenesis, serum angiogenic factors are ideal candidates as prognostic biomarkers.
Our 5-day evaluation indicated that all 16 assays in the panel had good reproducibility (total precisions over 5 independent plates in 5 days of <20%), adequate sensitivity (LOQs of majority of the assays less than 100 pg/ml), and wide dynamic ranges (linearity of majority of the assays spanning across 3 logs in concentrations).
Applying the panel to sera from prostate cancer patients with Gleason scores of 6, 7, 8-10, tumor stages that correlated with clinical outcome, we identified that the levels of sTIE-2, a soluble form of the transmembrane tyrosine kinase receptor for angiopoietins, were increased in patients with Gleason score of 8-10. Future studies are necessary to determine whether sTIE-2 could be used as a prognostic biomarker for identifying aggressive prostate cancer.
用于发现生物标志物的检测方法应具有稳健性和高通量性，能够在足够长的时间内以良好的精密度分析足够数量的样本。
我们评估了 Bio-Plex Pro™ 人类癌症生物标志物面板 1 的分析性能，这是一种 16 plex 多重免疫测定法，用于对血管生成因子进行综合分析。由于前列腺癌的进展和转移是与血管生成密切相关的病理事件，因此血清血管生成因子是作为预后生物标志物的理想候选物。
我们为期 5 天的评估表明，该面板中的所有 16 种检测方法都具有良好的重现性（5 天内 5 个独立板的总精密度均<20%）、足够的灵敏度（大多数检测方法的 LOQ 均小于 100pg/ml）和宽动态范围（大多数检测方法的线性范围跨越 3 个浓度对数）。
将该面板应用于与临床结果相关的 Gleason 评分分别为 6、7、8-10 的前列腺癌患者的血清中，我们发现，sTIE-2（血管生成素的跨膜酪氨酸激酶受体的可溶性形式）的水平在 Gleason 评分 8-10 的患者中增加。需要进一步的研究来确定 sTIE-2 是否可以用作识别侵袭性前列腺癌的预后生物标志物。
