Blood-based biomarkers of aggressive prostate cancer.

Abstract

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.

• Authors: Men Long Liong, Chun Ren Lim, Hengxuan Yang, Samuel Chao, Chin Wei Bong, Wing Seng Leong, Prashanta Kumar Das, Chit Sin Loh, Ban Eng Lau, Choon Geok Yu, Edie Jian Jiek Ooi, Robert K Nam, Paul D Allen, Graeme S Steele, Karl Wassmann, Jerome P Richie, Choong Chin Liew
• Journal: PloS one (PLoS One) Vol. 7 Issue 9 Pg. e45802 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23071848 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• Biomarkers, Tumor

Topics

• Aged
• Area Under Curve
• Biomarkers, Tumor (blood)
• Case-Control Studies
• Gene Expression Profiling
• Humans
• Logistic Models
• Malaysia
• Male
• Microarray Analysis
• Middle Aged
• Neoplasm Grading
• North America
• Prostatic Neoplasms (blood, diagnosis)
• ROC Curve
• Real-Time Polymerase Chain Reaction