Blood-Based Biomarkers of Aggressive Prostate Cancer

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

Comparative effectiveness and safety of various treatment procedures for lower pole renal calculi: a systematic review and network meta-analysis

To compare the effectiveness of various treatments used for lower pole renal calculi.We searched PubMed, EMBASE, CINAHL, the Cochrane Collaboration's Database of Systematic Reviews, the Cochrane Collaboration Central Register of Controlled Clinical Trials as well as ClinicalTrials.gov for reports up to 1 April 2014. The search was supplemented with abstract reports from various urology conferences. All randomised, 'blinded' clinical studies including patients treated for lower pole renal calculi o

High grade prostate cancer (Gleason score 8 and above) biomarker gene list and differential expression ratio in Cohort II verification sample set (80 disease and 102 controls).

<p># The 7 biomarkers were picked up from the 10 that were verified in Cohort II samples, using gene-ratio algorithm, based on the best AUC of combined gene-pair.</p>†<p>Determined by qRT-PCR analysis using SAMSN1 as a partner gene, gene ratio was calculated using delta delta Ct calculation.</p>‡<p>Calculated by Mann-Whitney test.</p>*<p>area under receiver-operating-characteristic curve.</p

PCR data from a sample set of 122 PAXgene samples of prostate cancer from the G8 group and 138 PAXgene samples from the control group were performed in a 1000×2-fold cross-validation test.

<p>Histograms of AUC were plotted and compared; results showed AUCs from the PCR data were well separated from the null sets, with an overlap of less than 5%.</p