Molecular Urology Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Clin Chim Acta. 2012 Mar 22;413(5-6):561-7. doi: 10.1016/j.cca.2011.11.027. Epub 2011 Nov 29.
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.
血清前列腺特异抗原（PSA）浓度缺乏特异性，无法区分前列腺癌与良性前列腺增生（BPH），导致不必要的活检。我们确定了 5 种针对特定癌症靶标的自身抗体特征，这些特征可能能够区分血清 PSA 升高的患者中的前列腺癌与 BPH。
为了确定自身抗体特征作为生物标志物，使用了天然抗原反向捕获微阵列平台。简要地，将经过充分表征的单克隆抗体排列在纳米颗粒载玻片上，以从前列腺癌细胞中捕获天然抗原。获得了 41 名前列腺癌患者和 39 名 BPH 患者（从首次诊断时开始收集）的血清样本，平均随访 6.56 年，没有癌症诊断（n=39）。从每位患者中纯化 100μg IgG，并标记 Cy3 染料，然后在阵列上孵育。扫描阵列以获取荧光，并对强度进行定量。生成接收者操作特征曲线，并确定曲线下面积（AUC）。
使用我们的微阵列平台，我们确定了能够区分前列腺癌和 BPH 的自身抗体特征。排名前 5 的自身抗体特征是 TARDBP、TLN1、PARK7、LEDGF/PSIP1 和 CALD1。将这些特征组合在一起，AUC 为 0.95（80%特异性时的敏感性为 95%），而血清浓度 PSA 的 AUC 为 0.5（80%特异性时的敏感性为 12.2%）。
我们的初步结果表明，我们能够识别出能够区分前列腺癌与 BPH 的特定自身抗体特征，可能会减少血清 PSA 升高患者中不必要的活检。
