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Open Access Highly Accessed Research

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

Chong Xie1, Hyun J Kim2, Jonathan G Haw3, Anusha Kalbasi3, Brian K Gardner4, Gang Li5, Jianyu Rao6, David Chia6, Monty Liong7, Rubio R Punzalan8, Leonard S Marks3, Allan J Pantuck3, Alexandre de la Taille9, Guomin Wang1, Hideki Mukouyama10 and Gang Zeng3*

Author Affiliations

1 Department of Urology, Zhongshan Hospital of Fudan University, No.180 Fenglin Road, Shanghai 200032, China

2 Department of Radiology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095-1721, USA

3 Department of Urology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095-1738, USA

4 Department of Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095-1732, USA

5 Department of Biostatistics, UCLA School of Public Health, 10833 Le Conte Ave, Los Angeles, CA 90095-1772, USA

6 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095-1738, USA

7 Department of Chemistry and Biochemistry, 607 Charles E. Young Drive East, Los Angeles, CA 90095-1569, USA

8 Advanced Medical Analysis, LLC, 1941 Walker Ave, Monrovia, CA 91016, USA

9 Department of Urology, CHU Henri Mondor, Créteil U955 E907, France

10 Department of Urology, Okinawa Nambu Tokushukai Hospital, 80 Hokama, Yaese-cho, Shimajiri-gun, Okinawa 901-0417, Japan

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Journal of Translational Medicine 2011, 9:43  doi:10.1186/1479-5876-9-43

Published: 19 April 2011

Abstract

Background

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).

Methods

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.

Results

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.

Conclusions

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.