Autoantibody signatures as biomarkers to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate specific antigen.

Autoantibody signatures as biomarkers to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate specific antigen.
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DOI:
10.1016/j.cca.2011.11.027
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发表时间:
2012-03-22
期刊:
Clinica chimica acta; international journal of clinical chemistry
影响因子:
--
通讯作者:
Liu BC
Liu BC
中科院分区:
其他
文献类型:
--
作者:
O'Rourke DJ;DiJohnson DA;Caiazzo RJ Jr;Nelson JC;Ure D;O'Leary MP;Richie JP;Liu BC

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血清前列腺特异性抗原(PSA)浓度缺乏区分前列腺癌和良性前列腺增生(BPH)的特异性,导致不必要的活检。我们确定了5种针对特定癌症靶点的自身抗体标记,这些标记可能能够在血清PSA升高的患者中区分前列腺癌和BPH。为了鉴定作为生物标志物的自身抗体特征,使用天然抗原反向捕获微阵列平台。简言之,将充分表征的单克隆抗体排列在纳米颗粒载玻片上以捕获来自前列腺癌细胞的天然抗原。获得了前列腺癌患者血清样品(n=41)和BPH患者样品(在初始诊断时开始收集),平均随访时间为6.56年,未诊断出癌症(n=39)。纯化100微克IgG并用Cy 3染料标记并在阵列上孵育。扫描阵列的荧光并定量强度。产生受试者工作特征曲线,并测定曲线下面积(AUC)。使用我们的微阵列平台,我们鉴定了能够区分前列腺癌和BPH的自身抗体特征。前5个自身抗体特征是TARDBP、TLN 1、PARK 7、LEDGF/PSIP 1和CALD 1。将这些特征组合导致AUC为0.95(灵敏度为95%,特异性为80%),而血清浓度PSA的AUC为0.5(灵敏度为12.2%,特异性为80%)。我们的初步结果表明,我们能够识别出可以区分前列腺癌和BPH的特异性自身抗体特征,并可能减少血清PSA升高患者不必要的活检。
Serum prostate specific antigen (PSA) concentrations lack the specificity to differentiate prostate cancer from benign prostate hyperplasia (BPH), resulting in unnecessary biopsies. We identified 5 autoantibody signatures to specific cancer targets which might be able to differentiate prostate cancer from BPH in patients with increased serum PSA. To identify autoantibody signatures as biomarkers, a native antigen reverse capture microarray platform was used. Briefly, well-characterized monoclonal antibodies were arrayed onto nanoparticle slides to capture native antigens from prostate cancer cells. Prostate cancer patient serum samples (n=41) and BPH patient samples (collected starting at the time of initial diagnosis) with a mean follow-up of 6.56 y without the diagnosis of cancer (n=39) were obtained. One hundred micrograms of IgGs were purified and labeled with a Cy3 dye and incubated on the arrays. The arrays were scanned for fluorescence and the intensity was quantified. Receiver operating characteristic curves were produced and the area under the curve (AUC) was determined. Using our microarray platform, we identified autoantibody signatures capable of distinguishing between prostate cancer and BPH. The top 5 autoantibody signatures were TARDBP, TLN1, PARK7, LEDGF/PSIP1, and CALD1. Combining these signatures resulted in an AUC of 0.95 (sensitivity of 95% at 80% specificity) compared to AUC of 0.5 for serum concentration PSA (sensitivity of 12.2% at 80% specificity). Our preliminary results showed that we were able to identify specific autoantibody signatures that can differentiate prostate cancer from BPH, and may result in the reduction of unnecessary biopsies in patients with increased serum PSA.
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