Prostate cancer (PCa) is a genetically heterogeneous cancer entity that causes challenges in pre-treatment clinical evaluation, such as the correct identification of the tumor stage. Conventional clinical tests based on digital rectal examination, Prostate-Specific Antigen (PSA) levels, and Gleason score still lack accuracy for stage prediction. We hypothesize that unraveling the molecular mechanisms underlying PCa staging via integrative analysis of multi-OMICs data could significantly improve the prediction accuracy for PCa pathological stages. We present a radiogenomic approach comprising clinical, imaging, and two genomic (gene and miRNA expression) datasets for 298 PCa patients. Comprehensive analysis of gene and miRNA expression profiles for two frequent PCa stages (T2c and T3b) unraveled the molecular characteristics for each stage and the corresponding gene regulatory interaction network that may drive tumor upstaging from T2c to T3b. Furthermore, four biomarkers (ANPEP, mir-217, mir-592, mir-6715b) were found to distinguish between the two PCa stages and were highly correlated (average r = ± 0.75) with corresponding aggressiveness-related imaging features in both tumor stages. When combined with related clinical features, these biomarkers markedly improved the prediction accuracy for the pathological stage. Our prediction model exhibits high potential to yield clinically relevant results for characterizing PCa aggressiveness.
Finite element (FE) modeling is widely used in biomechanical research, enabling computational investigations of anatomical structures. To develop accurate FE models, high-resolution medical imaging such as computed tomography (CT) is essential. However, CT exposes patients to ionizing radiation. Recently, radiation-free three-dimensional zero-echo-time magnetic resonance imaging (3D ZTE MRI) has shown promising results for bone visualization. Therefore, this feasibility study investigated whether 3D ZTE MRI is reliable for creating subject-specific FE models. Human femora from four female subjects were imaged using 3D ZTE MRI. Static FE analyses of the femora were performed in Abaqus/CAE, assuming a biphasic homogenous linear-elastic material. A sensitivity analysis was conducted to evaluate varying bone material properties. After loading with 2000 N, the mean displacement of the femoral head amounted to −1.30 ± 0.26 mm (vertical) and −9.03 ± 2.21 mm (horizontal), while the femoral neck exhibited compressive (inferior: −1366.03 ± 182.70 µm/m) and tensile (superior: 1038.69 ± 135.82 µm/m) strains. Overall, the results demonstrate displacement and strain predictions similar to previous experimental and computational studies based on CT data. Therefore, despite several simplifications, these findings confirm the feasibility of radiation-free 3D ZTE MRI for subject-specific FE modeling, enabling future simultaneous assessment of bone morphology and surrounding soft tissues.