Anti-Oligomannose Antibodies as Potential Serum Biomarkers of Aggressive Prostate Cancer
Version of Record online: 11 FEB 2013
© 2013 Wiley Periodicals, Inc.
Drug Development Research
Special Issue: Biomarkers in Drug Development and Companion Diagnostics
Volume 74, Issue 2, pages 65–80, March 2013
How to Cite
Wang, D., Dafik, L., Nolley, R., Huang, W., Wolfinger, R. D., Wang, L.-X. and Peehl, D. M. (2013), Anti-Oligomannose Antibodies as Potential Serum Biomarkers of Aggressive Prostate Cancer. Drug Dev. Res., 74: 65–80. doi: 10.1002/ddr.21063
- Issue online: 19 MAR 2013
- Version of Record online: 11 FEB 2013
- NCI/NIH. Grant Numbers: U01CA128416, U01CA128416-S2
- NIAID/NIH. Grant Number: R01 AI067111
- carbohydrate microarray;
- prostate cancer
This study bridges a carbohydrate microarray discovery and a large-scale serological validation of anti-oligomannose antibodies as novel serum biomarkers of aggressive prostate cancer (PCa). Experimentally, a Man9-cluster-specific enzyme-linked immunosorbent assay was established to enable sensitive detection of anti-Man9 antibodies in human sera. A large-cohort of men with PCa or benign prostatic hyperplasia (BPH) whose sera were banked at Stanford University was characterized using this assay. Subjects included patients with 100% Gleason grade 3 cancer (n = 84), with Gleason grades 4 and/or 5 cancer (n = 204), and BPH controls (n = 135). Radical prostatectomy Gleason grades and biochemical (PSA) recurrence served as key parameters for serum biomarker evaluation. It was found that IgGMan9 and IgMMan9 were widely present in the sera of men with BPH, as well as those with cancer. However, these antibody reactivities were significantly increased in the subjects with the largest volumes of high grade cancer. Detection of serum IgGMan9 and IgMMan9 significantly predicted the clinical outcome of PCa post-radical prostatectomy. Given these results, we suggest that IgGMan9 and IgMMan9 are novel serum biomarkers for monitoring aggressive progression of PCa. The potential of oligomannosyl antigens as targets for PCa subtyping and targeted immunotherapy is yet to be explored.