A novel multiplex assay combining autoantibodies plus PSA has potential implications for classification of prostate cancer from non-malignant cases

Journal of Translational Medicine

Research

Rubio R Punzalan¹  Gang Li²  Monty Liong³  Brian K Gardner⁴  David Chia⁵  Jianyu Rao⁵  Hyun J Kim⁶  Alexandre de la Taille⁷  Anusha Kalbasi⁸  Gang Zeng⁸  Jonathan G Haw⁸  Leonard S Marks⁸  Allan J Pantuck⁸  Hideki Mukouyama⁹  Guomin Wang^1,10  Chong Xie^1,10 

[1] Advanced Medical Analysis, LLC, 1941 Walker Ave, 91016, Monrovia, CA, USA;Department of Biostatistics, UCLA School of Public Health, 10833 Le Conte Ave, 90095-1772, Los Angeles, CA, USA;Department of Chemistry and Biochemistry, 607 Charles E. Young Drive East, 90095-1569, Los Angeles, CA, USA;Department of Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, 90095-1732, Los Angeles, CA, USA;Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, 90095-1738, Los Angeles, CA, USA;Department of Radiology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, 90095-1721, Los Angeles, CA, USA;Department of Urology, CHU Henri Mondor, U955 E907, Créteil, France;Department of Urology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, 90095-1738, Los Angeles, CA, USA;Department of Urology, Okinawa Nambu Tokushukai Hospital, 80 Hokama, Yaese-cho, Shimajiri-gun, 901-0417, Okinawa, Japan;Department of Urology, Zhongshan Hospital of Fudan University, No.180 Fenglin Road, 200032, Shanghai, China;

关键词: Prostate Cancer;    Prostate Specific Antigen;    Prostate Cancer Patient;    Prostatitis;    Multiplex Assay;   

DOI  :  10.1186/1479-5876-9-43

 received in 2011-02-09, accepted in 2011-04-19,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe 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).MethodsTo 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.ResultsPeptide 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.ConclusionsThe 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.

【 授权许可】

Unknown   
© Xie et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.