Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
Prostate. 2012 Mar;72(4):427-36. doi: 10.1002/pros.21444. Epub 2011 Jul 11.
The currently used prostate cancer serum marker has a low cancer specificity and improved diagnostics are needed. Here we evaluated whether autoantibodies are present in sera of prostate cancer patients and whether they are useful diagnostic markers for prostate cancer.
Sera from 20 prostate cancer patients and 20 healthy controls were incubated on expression clone arrays containing more than 37,000 recombinant human proteins. Functional annotation clustering of the identified autoantigens was performed using the DAVID database. Autoantigens identified in the prostate cancer group were validated on microarrays using sera of 40 prostate cancer patients, 40 patients with elevated PSA levels but prostate cancer negative biopsies (benign disease), and 40 healthy controls.
We detected autoantibodies against 408 different antigens in sera of prostate cancer patients. One hundred seventy-four of these were exclusively detected in the cancer group compared to the healthy control group. Functional annotation clustering revealed an enrichment of RNA-associated, cytoskeleton, and nuclear proteins. The autoantibody panel was validated in serum samples of independent prostate cancer patients. Autoantibody profiles discriminated between prostate cancer patients and benign disease patients with an ROC curve AUC of 0.71. TTLL12, a protein recently described to be over-expressed in prostate cancer, was the highest ranked discrimination autoantigen.
A variety of autoantibodies were identified in sera of prostate cancer patients and provide a first step towards autoantibody diagnostics. Serum autoantibodies reflect the disease and represent valuable tools not only for prostate cancer, but also for other diseases affecting the immune response.
目前使用的前列腺癌血清标志物具有较低的癌症特异性,因此需要改进诊断方法。本研究评估了前列腺癌患者的血清中是否存在自身抗体,以及它们是否可用作前列腺癌的诊断标志物。
将来自 20 例前列腺癌患者和 20 例健康对照者的血清与包含 37000 多个重组人蛋白的表达克隆阵列孵育。使用 DAVID 数据库对鉴定出的自身抗原进行功能注释聚类分析。使用来自 40 例前列腺癌患者、40 例 PSA 水平升高但前列腺癌活检阴性(良性疾病)患者和 40 例健康对照者的血清,在微阵列上验证在前列腺癌组中鉴定出的自身抗原。
我们在前列腺癌患者的血清中检测到针对 408 种不同抗原的自身抗体。其中 174 种仅在癌症组中与健康对照组相比被特异性检测到。功能注释聚类分析显示 RNA 相关、细胞骨架和核蛋白富集。该自身抗体面板在独立的前列腺癌患者的血清样本中进行了验证。自身抗体谱可将前列腺癌患者与良性疾病患者区分开来,ROC 曲线 AUC 为 0.71。TTLL12 是一种最近在前列腺癌中被描述为过度表达的蛋白质,是最高排名的鉴别自身抗原。
在前列腺癌患者的血清中鉴定出多种自身抗体,为自身抗体诊断迈出了第一步。血清自身抗体反映了疾病,不仅对前列腺癌,而且对其他影响免疫反应的疾病都具有重要的诊断价值。