Blood-Based Biomarkers of Aggressive Prostate Cancer

Abstract

PurposeProstate 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 MethodsBlood 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.ResultsMicroarray 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.ConclusionIn 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.

Diagnostic and Prognostic Scoring System for Prostate Cancer Using Urine and Plasma Biomarkers

“…The search of biomarkers for early detection of PCa has proved difficult and complicated (Liong et al, 2012). Detecting PCa is important, but it is also important to determine the aggressiveness of the cancer.…”

Prior cancer diagnosis in men with nonmetastatic prostate cancer and the risk of prostate cancer specific and all-cause mortality.

“…These results suggest that when a multidisciplinary team of physicians consult on a patient AS is more likely to be recommended. Second, investigators have attempted to define novel assays such as circulating tumor cell burden [22] and gene profiling [23,24] that can stratify patients with castration resistant PC into cohorts with longer or shorter median survivals. Such tools are needed in men with low-risk PC in order to more appropriately select men for AS.…”

Long-term differences in urinary, bowel and sexual function among men treated with surgery versus radiation for prostate cancer

“…8 Other groups have incorporated the use of multiparametric MRI and serum biomarkers to improve identification of patients at higher risk of prostate cancer death. 9,10 There are several important limitations of this study. Men were asked to recall their baseline urinary, sexual and bowel function prior to therapy at a time point 6 months after they had undergone treatment, a criticism of all Prostate Cancer Outcomes Study-based studies.…”