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Anti-Oligomannose Antibodies as Potential Serum Biomarkers of Aggressive Prostate Cancer.

ABSTRACT: [Table: see text] 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 IgG(Man9) and IgM(Man9) 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 IgG(Man9) and IgM(Man9) significantly predicted the clinical outcome of PCa post-radical prostatectomy. Given these results, we suggest that IgG(Man9) and IgM(Man9) 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.

SUBMITTER: Wang D

PROVIDER: S-EPMC4139012 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Anti-Oligomannose Antibodies as Potential Serum Biomarkers of Aggressive Prostate Cancer.

Wang Denong D Dafik Laila L Nolley Rosalie R Huang Wei W Wolfinger Russell D RD Wang Lai-Xi LX Peehl Donna M DM

Drug development research 20130301 2

[Table: see text] 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 ...[more]

PMID: 25152555

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Project description:PURPOSE: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. MATERIALS AND METHODS: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR) analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. RESULTS: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ?8) and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ?8) 55% of G6 samples, 49% of G7(3+4), 79% of G7(4+3) and 83% of G8-10, while rejecting 98% of controls. CONCLUSION: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from biopsy and immediate therapy versus those more suited to an "active surveillance" strategy.

Dataset Information

Anti-Oligomannose Antibodies as Potential Serum Biomarkers of Aggressive Prostate Cancer.

Publications

Anti-Oligomannose Antibodies as Potential Serum Biomarkers of Aggressive Prostate Cancer.

Similar Datasets

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