Purpose
Liquid biopsies that noninvasively detect molecular correlates of aggressive prostate cancer (PCa) could be used to triage patients, reducing the burdens of unnecessary invasive prostate biopsy and enabling early detection of high-risk disease. DNA hypermethylation is among the earliest and most frequent aberrations in PCa. We investigated the accuracy of a six-gene DNA methylation panel (Epigenetic Cancer of the Prostate Test in Urine [epiCaPture]) at detecting PCa, high-grade (Gleason score greater than or equal to 8) and high-risk (D’Amico and Cancer of the Prostate Risk Assessment] PCa from urine.
Patients and Methods
Prognostic utility of epiCaPture genes was first validated in two independent prostate tissue cohorts. epiCaPture was assessed in a multicenter prospective study of 463 men undergoing prostate biopsy. epiCaPture was performed by quantitative methylation-specific polymerase chain reaction in DNA isolated from prebiopsy urine sediments and evaluated by receiver operating characteristic and decision curves (clinical benefit). The epiCaPture score was developed and validated on a two thirds training set to one third test set.
Results
Higher methylation of epiCaPture genes was significantly associated with increasing aggressiveness in PCa tissues. In urine, area under the receiver operating characteristic curve was 0.64, 0.86, and 0.83 for detecting PCa, high-grade PCa, and high-risk PCa, respectively. Decision curves revealed a net benefit across relevant threshold probabilities. Independent analysis of two epiCaPture genes in the same clinical cohort provided analytical validation. Parallel epiCaPture analysis in urine and matched biopsy cores showed added value of a liquid biopsy.
Conclusion
epiCaPture is a urine DNA methylation test for high-risk PCa. Its tumor specificity out-performs that of prostate-specific antigen (greater than 3 ng/mL). Used as an adjunct to prostate-specific antigen, epiCaPture could aid patient stratification to determine need for biopsy.
Our research aims to develop a shear forming envelope for the preforming of textiles, a critical step in the manufacture of fibre-reinforced composite materials. This paper demonstrates the progress towards this aim by conducting picture frame tests to empirically determine the locking angle of non-crimp fabrics with different fibre orientations. While conventional shear tests typically utilise woven textile samples with orthogonal fibre directions of 0°/90°, the investigation of non-crimp fabrics, especially with non-standard fibre orientations, is less common. As a result, there is little knowledge about the shear deformation behaviour of these fabric types, despite their relevance to the aerospace industry. In this study, the shear locking angles of various carbon fibre non-crimp fabrics are investigated, gradually reducing the relative fibre angles of the textile materials from ±45° to ±22.5°. Previously, it was observed that unidirectional 0° reinforcement layers induce draping defects when forming multiaxial non-crimp fabric stacks into curved aerospace stiffeners. Their substitution by reinforcements with smaller cross-ply angles such as ±30° resulted in better formability and reduced defects. It is however unclear, how the shear locking angle decreases with more acute cross-ply angles. Here, we report for the first time a correlation between the fibre orientation of the non-crimp fabric and its shear locking angle. The resulting shear forming envelope provides composite design and manufacturing guidance for an enhanced utilisation of the advantageous but anisotropic properties of carbon fibre textiles.
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