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A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra.

ABSTRACT: A comprehensive cellular anatomy of normal human prostate is essential for solving the cellular origins of benign prostatic hyperplasia and prostate cancer. The tools used to analyze the contribution of individual cell types are not robust. We provide a cellular atlas of the young adult human prostate and prostatic urethra using an iterative process of single-cell RNA sequencing (scRNA-seq) and flow cytometry on ?98,000 cells taken from different anatomical regions. Immunohistochemistry with newly derived cell type-specific markers revealed the distribution of each epithelial and stromal cell type on whole mounts, revising our understanding of zonal anatomy. Based on discovered cell surface markers, flow cytometry antibody panels were designed to improve the purification of each cell type, with each gate confirmed by scRNA-seq. The molecular classification, anatomical distribution, and purification tools for each cell type in the human prostate create a powerful resource for experimental design in human prostate disease.

SUBMITTER: Henry GH

PROVIDER: S-EPMC6411034 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra.

Henry Gervaise H GH Malewska Alicia A Joseph Diya B DB Malladi Venkat S VS Lee Jeon J Torrealba Jose J Mauck Ryan J RJ Gahan Jeffrey C JC Raj Ganesh V GV Roehrborn Claus G CG Hon Gary C GC MacConmara Malcolm P MP Reese Jeffrey C JC Hutchinson Ryan C RC Vezina Chad M CM Strand Douglas W DW

Cell reports 20181201 12

A comprehensive cellular anatomy of normal human prostate is essential for solving the cellular origins of benign prostatic hyperplasia and prostate cancer. The tools used to analyze the contribution of individual cell types are not robust. We provide a cellular atlas of the young adult human prostate and prostatic urethra using an iterative process of single-cell RNA sequencing (scRNA-seq) and flow cytometry on ∼98,000 cells taken from different anatomical regions. Immunohistochemistry with new ...[more]

PMID: 30566875

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Project description:Rationale and objectiveThe combined use of prostate cancer radiotherapy and MRI planning is increasingly being used in the treatment of clinically significant prostate cancers. The radiotherapy dosage quantity is limited by toxicity in organs with de-novo genitourinary toxicity occurrence remaining unperturbed. Estimation of the urethral radiation dose via anatomical contouring may improve our understanding of genitourinary toxicity and its related symptoms. Yet, urethral delineation remains an expert-dependent and time-consuming procedure. In this study, we aim to develop a fully automated segmentation tool for the prostatic urethra.Materials and methodsThis study incorporated 939 patients' T2-weighted MRI scans (train/validation/test/excluded: 657/141/140/1 patients), including in-house and public PROSTATE-x datasets, and their corresponding ground truth urethral contours from an expert genitourinary radiologist. The AI model was developed using MONAI framework and was based on a 3D-UNet. AI model performance was determined by Dice score (volume-based) and the Centerline Distance (CLD) between the prediction and ground truth centers (slice-based). All predictions were compared to ground truth in a systematic failure analysis to elucidate the model's strengths and weaknesses. The Wilcoxon-rank sum test was used for pair-wise comparison of group differences.ResultsThe overall organ-adjusted Dice score for this model was 0.61 and overall CLD was 2.56 mm. When comparing prostates with symmetrical (n = 117) and asymmetrical (n = 23) benign prostate hyperplasia (BPH), the AI model performed better on symmetrical prostates compared to asymmetrical in both Dice score (0.64 vs. 0.51 respectively, p < 0.05) and mean CLD (2.3 mm vs. 3.8 mm respectively, p < 0.05). When calculating location-specific performance, the performance was highest at the apex and lowest at the base location of the prostate for Dice and CLD. Dice location dependence: symmetrical (Apex, Mid, Base: 0.69 vs. 0.67 vs. 0.54 respectively, p < 0.05) and asymmetrical (Apex, Mid, Base: 0.68 vs. 0.52 vs. 0.39 respectively, p < 0.05). CLD location dependence: symmetrical (Apex, Mid, Base: 1.43 mm vs. 2.15 mm vs. 3.28 mm, p < 0.05) and asymmetrical (Apex, Mid, Base: 1.83 mm vs. 3.1 mm vs. 6.24 mm, p < 0.05).ConclusionWe developed a fully automated prostatic urethra segmentation AI tool yielding its best performance in prostate glands with symmetric BPH features. This system can potentially be used to assist treatment planning in patients who can undergo whole gland radiation therapy or ablative focal therapy.

Dataset Information

A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra.

Publications

A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra.

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