Citations

Introduction: Abdominal aortic aneurysms (AAA) are common among individuals over age 65 with a prevalence of 9%. Most AAAs are small and require surveillance imaging to monitor size and growth rates. Tools capable of predicting growth rates would be clinically useful. Hypothesis: We investigated how computational hemodynamics derived from CT angiography (CTA) differentiated slow and rapid-growing AAAs. Methods: Using readily available computing power in the clinical workflow, 3D models were generated for 25 subjects with AAA from available 3D CTA data. AAA growth rates were categorized as slow ( less than 5 mm/year) or rapid (greater than 5 mm/year) based on serial imaging. A geometrical analysis was performed using 7 indices (Volume, Surface Area, Length, Max/Min radius, Expansion Ratio [Mean radius/vessel radius], Proximal vessel area, Voronoi diagram-based metrics) for each AAA. Computational hemodynamics were performed using commercial software (ANSYS-Fluent). Computational hemodynamics were completed for all cases (see Fig. 1). In-house software assessed wall shear stress-(WSS) and vortex-based hemodynamics. Support vector machine (SVM) was run with cross-validation (50 iterations) to assess predictive strength using these 16 parameters. Results: Among 25 AAAs studied, 7 were rapid and 18 were slow-growing. The combination of proximal vessel area, spatiotemporally averaged WSS, and spatially averaged OSI provided the best accuracy for growth differentiation. The area under receiving operating curve (AUROC) and total accuracy are 0.770 and 0.765, respectively, with 48% and 86% of rapid and slow-growing AAAs correctly identified, respectively. Conclusions: Computational hemodynamics appears feasible with reasonable growth rate prediction. With optimization, this tool may enable resource utilization refinement for imaging surveillance strategies by distinguishing rapid from slow-growing AAAs.

Abstract Prostate cancer (CaP) is a heterogeneous disease characterized by features of non-aggressive, slow-growing disorders to fast-growing disease. Men of African ancestry have disproportionately higher incidence and mortality rates for CaP than men of European ancestry. While there is evidence for a higher genetic predisposition for incidence of CaP in men of African ancestry compared to men of European ancestry, there is paucity of molecular biology and transcriptomic studies on the role of Human endogenous retroviruses (HERVs) in relation to CaP-associated genes in CaP pathogenesis and prognosis. In this study, we performed bulk RNA sequencing (RNA-seq) on formalin-fixed paraffin-embeded (FFPE) CaP samples from Nigerian CaP patients to investigate the expression significance of HERV-R in relation to FOXA1, TMPRSS2, BAZ1B, KMT2D, ATF4 and BRAF genes. Based on this findings, we used immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) to confirm the expression pattern of the HERV-R and FOXA1, TMPRSS2, BAZ1B, KMT2D, ATF4 and BRAF proteins on 45 FFPE CaP and blood plasma samples, and 5 CaP-free samples from patients in Zaria, Nigeria. Most of these patients were longitudinally followed from 2017 to date. The DESeq2 procedure was used for data processing, analysis, and differential expression analysis of the aforementioned genes. We found a significant expression of HERV-R in relation with FOXA1, TMPRSS2, BAZ1B, KMT2D, ATF4, CCND1 and BRAF in the CaP from rural Africans in Nigeria. HERV-R expression was found to be associated with increased PSA level, higher Gleason grade and poor prognosis of CaP. A CaP sample from an 80-year-old patient that was histologically diagnosed to have no malignancy seen despite high PSA level of >100 and poor disease outcomes shows a significant cytoplasmic expression of HERV-R, indicating that HERV-R may serve as an important biomarker for early detection. Unfortunately, we lost the 80-year-old patient to late detection before revisiting his case for proper histological diagnosis and management. In addition, some histologically diagnosed BPH samples that are apparently reported to be CaP-free show stromal cells expression of HERV-R and in some cases show expression of HERV-R in the prostatic glandular areas. In contrast, stromal cells of the CaP samples show no expression of HERV-R, but strong expression in the glandular areas. This may implicate a gradual transition from benign prostatic lesion to malignant prostatic disease. HERV-R expression in CaP may have a relationship with BRAF, CCND1, FOXA1, TMPRSS2 and ATF4 genes. These findings combined together, underscore the importance of the expanded concept of HERV-R expression and CaP associated genes in early detection of CaP and prognosis. Citation Format: Faruk Mohammed, Konrad Stawiski, Halimatu Sadiya Musa, Sani Kamarudeen Owolabi, Sani Abubakar, Solomon O. Rotimi, Adoke Kasimu Umar, Yawale Iliyasu, Ahmad Bello, Folakemi T. Odedina, Clayton C. Yates, Kevin Petrie, Franklin W. Huang, Sani Ibrahim. Co-expression of HERV-R, CCND1, BRAF, FOXA1, TMPRSS2, ATF4 and low expression of BAZ1B and KMT2D is associated with early detection and poor prognosis of prostate cancer in African Black men from Nigeria [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6432.