Department of Urology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095-1738, USA.
J Transl Med. 2011 Apr 19;9:43. doi: 10.1186/1479-5876-9-43.
The lack of sufficient specificity and sensitivity among conventional cancer biomarkers, such as prostate specific antigen (PSA) for prostate cancer has been widely recognized after several decades of clinical implications. Autoantibodies (autoAb) among others are being extensively investigated as potential substitute markers, but remain elusive. One major obstacle is the lack of a sensitive and multiplex approach for quantifying autoAb against a large panel of clinically relevant tumor-associated antigens (TAA).
To circumvent preparation of phage lysates and purification of recombinant proteins, we identified B cell epitopes from a number of previously defined prostate cancer-associated antigens (PCAA). Peptide epitopes from cancer/testis antigen NY-ESO-1, XAGE-1b, SSX-2,4, as well as prostate cancer overexpressed antigen AMACR, p90 autoantigen, and LEDGF were then conjugated with seroMAP microspheres to allow multiplex measurement of autoAb present in serum samples. Moreover, simultaneous quantification of autoAb plus total PSA was achieved in one reaction, and termed the "A+PSA" assay.
Peptide epitopes from the above 6 PCAA were identified and confirmed that autoAb against these peptide epitopes reacted specifically with the full-length protein. A pilot study was conducted with the A+PSA assay using pre-surgery sera from 131 biopsy-confirmed prostate cancer patients and 121 benign prostatic hyperplasia and/or prostatitis patients. A logistic regression-based A+PSA index was found to enhance sensitivities and specificities over PSA alone in distinguishing prostate cancer from nonmalignant cases. The A+PSA index also reduced false positive rate and improved the area under a receiver operating characteristic curve.
The A+PSA assay represents a novel platform that integrates autoAb signatures with a conventional cancer biomarker, which may aid in the diagnosis and prognosis of prostate cancer and others.
经过几十年的临床应用，人们已经广泛认识到传统癌症生物标志物（如前列腺特异性抗原 [PSA]）缺乏足够的特异性和敏感性。除其他外，自身抗体（autoAb）正被广泛研究作为潜在的替代标志物，但仍难以捉摸。一个主要障碍是缺乏一种敏感且多重的方法来定量针对大量临床相关肿瘤相关抗原（TAA）的自身抗体。
为了避免制备噬菌体裂解物和纯化重组蛋白，我们从一些先前定义的前列腺癌相关抗原（PCAA）中鉴定了 B 细胞表位。来自癌症/睾丸抗原 NY-ESO-1、XAGE-1b、SSX-2、4 的肽表位，以及前列腺癌过表达抗原 AMACR、p90 自身抗原和 LEDGF 与 seroMAP 微球缀合，以允许对血清样本中存在的自身抗体进行多重测量。此外，在一个反应中同时实现了自身抗体加总 PSA 的定量，称为“A+PSA”测定。
鉴定了来自上述 6 个 PCAA 的肽表位，并证实了针对这些肽表位的自身抗体与全长蛋白特异性反应。使用 131 例经活检证实的前列腺癌患者和 121 例良性前列腺增生和/或前列腺炎患者的术前血清进行了 A+PSA 测定的初步研究。发现基于逻辑回归的 A+PSA 指数在区分前列腺癌与非恶性病例方面优于 PSA 单独使用时的灵敏度和特异性。A+PSA 指数还降低了假阳性率并提高了接收器操作特性曲线下的面积。
A+PSA 测定代表了一种新的平台，该平台将自身抗体特征与传统癌症生物标志物相结合，可能有助于前列腺癌和其他癌症的诊断和预后。
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