A novel multiplex assay combining autoantibodies plus PSA has potential implications for classification of prostate cancer from non-malignant cases.
A novel multiplex assay combining autoantibodies plus PSA has potential implications for classification of prostate cancer from non-malignant cases.
复制标题
DOI：
10.1186/1479-5876-9-43
复制
发表时间：
2011-04-19
影响因子：
7.4
通讯作者：
Zeng G
中科院分区：
文献类型：
--
作者：
Xie C;Kim HJ;Haw JG;Kalbasi A;Gardner BK;Li G;Rao J;Chia D;Liong M;Punzalan RR;Marks LS;Pantuck AJ;de la Taille A;Wang G;Mukouyama H;Zeng G
经过几十年的临床应用后，人们广泛认识到传统癌症生物标志物（例如前列腺癌的前列腺特异性抗原（PSA））缺乏足够的特异性和灵敏度。自身抗体（autoAb）作为潜在的替代标记物正在被广泛研究，但仍然难以捉摸。一个主要的障碍是缺乏一个敏感的和多重的方法来定量针对一个大的面板的临床相关的肿瘤相关抗原（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，我们从许多以前定义的前列腺癌相关抗原（PCAA）中鉴定了B细胞表位。然后将来自癌症/睾丸抗原NY-ESO-1、XAGE-1b、SSX-2，4以及前列腺癌过表达抗原AMACR、p90自身抗原和LEDGF的肽表位与seroMAP微球缀合，以允许多重测量血清样品中存在的自身抗体。此外，在一个反应中实现autoAb加总PSA的同时定量，并称为“A+PSA”测定。鉴定了来自上述6种PCAA的肽表位，并证实针对这些肽表位的autoAb与全长蛋白特异性反应。使用来自131名经活检证实的前列腺癌患者和121名良性前列腺增生和/或前列腺炎患者的术前血清进行A+PSA测定的初步研究。基于Logistic回归的A+PSA指数在区分前列腺癌和非恶性病例中的敏感性和特异性高于单独的PSA。A+PSA指数也降低了假阳性率，改善了受试者工作特征曲线下面积。A+PSA检测代表了一种新的平台，它将autoAb特征与传统的癌症生物标志物相结合，这可能有助于前列腺癌和其他癌症的诊断和预后。
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.
登录
查看更多内容
影响因子：
4
作者：
Zehentner, Barbara K.;Secrist, Heather;Houghton, Raymond L.
通讯作者：
Houghton, Raymond L.
影响因子：
6.4
作者：
Zeng, G;Aldridge, ME;Belldegrun, AS
通讯作者：
Belldegrun, AS
影响因子：
10.3
作者：
Bouwhuis, Marna G.;Suciu, Stefan;Eggermont, Alexander M. M.
通讯作者：
Eggermont, Alexander M. M.
影响因子：
6.4
作者：
Stone, B;Schummer, M;Nelson, BH
通讯作者：
Nelson, BH
影响因子：
2.8
作者：
Dubovsky, Jason A.;McNeel, Douglas G.
通讯作者：
McNeel, Douglas G.