Expression Patterns of ERα, ERβ, AR, SIRT1, SIRT2, and SIRT3 in Prostate Cancer Tissue and Normal Prostate Tissue

298 Background: We previously found that vasectomy was associated with an increased risk of prostate cancer, and particularly, risk of lethal prostate cancer in the Health Professionals Follow-up Study (HPFS). However, the possible biological basis for this finding is unclear. In this study, we explored possible biological mechanisms by assessing differences in gene expression in the prostate tissue of men with and without a history of vasectomy prostate cancer diagnosis. Methods: Within the HPFS, vasectomy data and gene expression data (20,254 genes) was available from archival tumor tissue from 263 cases, 124 of whom also had data for adjacent normal tissue. To relate expression of individual genes to vasectomy we used linear regression adjusting for age and year at diagnosis. We ran gene set enrichment analysis to identify pathways of genes associated with vasectomy. Results: Among 263 cases, 67 (25%) reported a vasectomy prior to cancer diagnosis. Mean age at diagnosis was 66 years among men without and 65 years among men with vasectomy. Median time between vasectomy and prostate cancer diagnosis was 25 years. Gene expression in tumor tissue was not associated with vasectomy status. In adjacent normal tissue, three individual genes were associated with vasectomy with Bonferroni-corrected p-values of < 0.10: RAPGEF6, OR4C3, and SLC35F4. Gene set enrichment analysis found five pathways upregulated and seven pathways downregulated in men with vasectomy compared to those without in normal prostate tissue with a FDR < 0.05. Upregulated pathways included several immune-related gene sets and G-protein-coupled receptor gene sets. Conclusions: We identified significant differences in gene expression profiles in normal prostate tissue according to vasectomy status among men treated for prostate cancer. The fact that such differences existed several decades after vasectomy provides support for the idea that vasectomy may play a role in the etiology of prostate cancer.

Download Full-text

Multispectral Photoacoustic Imaging of Prostate Cancer: Preliminary Ex-vivo Results

Journal of Clinical Imaging Science ◽

10.4103/2156-7514.119139 ◽

2013 ◽

Vol 3 ◽

pp. 41 ◽

Cited By ~ 49

Author(s):

Vikram S. Dogra ◽

Bhargava K. Chinni ◽

Keerthi S. Valluru ◽

Jean V. Joseph ◽

Ahmed Ghazi ◽

...

Keyword(s):

Prostate Cancer ◽

Predictive Value ◽

Ex Vivo ◽

Prostate Tissue ◽

Human Prostate ◽

Normal Prostate ◽

Mean Intensity ◽

Preliminary Results ◽

Normal Prostate Tissue ◽

Malignant Prostate

Objective: The objective of this study is to validate if ex-vivo multispectral photoacoustic (PA) imaging can differentiate between malignant prostate tissue, benign prostatic hyperplasia (BPH), and normal human prostate tissue. Materials and Methods: Institutional Review Board's approval was obtained for this study. A total of 30 patients undergoing prostatectomy for biopsy-confirmed prostate cancer were included in this study with informed consent. Multispectral PA imaging was performed on surgically excised prostate tissue and chromophore images that represent optical absorption of deoxyhemoglobin (dHb), oxyhemoglobin (HbO2), lipid, and water were reconstructed. After the imaging procedure is completed, malignant prostate, BPH and normal prostate regions were marked by the genitourinary pathologist on histopathology slides and digital images of marked histopathology slides were obtained. The histopathology images were co-registered with chromophore images. Region of interest (ROI) corresponding to malignant prostate, BPH and normal prostate were defined on the chromophore images. Pixel values within each ROI were then averaged to determine mean intensities of dHb, HbO2, lipid, and water. Results: Our preliminary results show that there is statistically significant difference in mean intensity of dHb (P < 0.0001) and lipid (P = 0.0251) between malignant prostate and normal prostate tissue. There was difference in mean intensity of dHb (P < 0.0001) between malignant prostate and BPH. Sensitivity, specificity, positive predictive value, and negative predictive value of our imaging system were found to be 81.3%, 96.2%, 92.9% and 89.3% respectively. Conclusion: Our preliminary results of ex-vivo human prostate study suggest that multispectral PA imaging can differentiate between malignant prostate, BPH and normal prostate tissue.

Download Full-text

Erratum: Corrigendum: Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue

Nature Genetics ◽

10.1038/ng0615-689b ◽

2015 ◽

Vol 47 (6) ◽

pp. 689-689 ◽

Cited By ~ 4

Author(s):

Colin S Cooper ◽

◽

Rosalind Eeles ◽

David C Wedge ◽

Peter Van Loo ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Tissue ◽

Normal Prostate ◽

Normal Prostate Tissue

Download Full-text

Integrated-omics of MRI-visible and -invisible prostate cancer identifies molecular correlations with clinical outcome.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17506 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17506-e17506

Author(s):

Eric Kim ◽

Natalia Miheecheva ◽

Akshaya Ramachandran ◽

Yang Lyu ◽

Ilia Galkin ◽

...

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Cell Density ◽

Malignant Cell ◽

Prostate Tissue ◽

Malignant Cells ◽

Normal Prostate ◽

Normal Prostate Tissue ◽

Clinically Significant ◽

Wasserstein Distances

e17506 Background: The inclusion of multiparametric MRI (mpMRI) to prostate cancer (PCa) diagnostics has increased the detection rate and has improved the prediction rate of clinically significant PCa. Yet, mpMRI has a false negative rate of 12.6%, missing 6-13% of clinically significant PCa. The mechanisms underlying MRI visibility are poorly understood; therefore, to probe the molecular and cellular underpinnings of PCa MRI visibility, we profiled tissue from Gleason score and clinically matched patients with MRI-visible and MRI-invisible PCa who underwent radical prostatectomy. Methods: MRI-invisible (n = 7) and MRI-visible (n = 8) PCa tumors were evaluated with multiplex immunofluorescence (MxIF; 14 markers) and were subjected to gene expression profiling using the HTG EdgeSeq Oncology Biomarker Panel (2,549 genes). Gene expression analysis was also performed using The Cancer Genome Atlas (TCGA), including normal prostate (n = 52) and PCa (n = 387) tissue. Analyses were performed using the BostonGene automated pipeline. Results: MpMRI-visible PCa tumors (62.5%) displayed compact epithelial tumor architecture compared with mpMRI-invisible PCa tumors (28.5%). mpMRI-visible PCa had higher malignant cell density (p = 0.04) and increased neighboring malignant cells (p = 0.07), correlating with MRI-visible PCa complex tumor architecture (r = 0.49 for neighboring malignant cells vs tumor cell density). Tumor stromal organization differences were determined by measuring Wasserstein distances between distributions, and mpMRI-invisible PCa stroma appeared more similar to normal tissue. The visible group exhibited lower expression of stroma-enriched genes such as filamin C (FLNC) (FDR < 0.1) and cellular adhesion-related genes (FDR < 0.4), with gene expression signatures markedly different compared to normal prostate tissue. Higher malignant cell density, neighboring malignant cells, and Wasserstein distances, and low FLNC expression – all mpMRI visibility characteristics – were associated with patient relapse (p = 0.02). Low stroma signature expression in the TCGA cohort correlated with inferior PCa PFS (p = 0.005). Conclusions: This is the first integrated multi-omics analysis of clinically matched mpMRI-visible and -invisible PCa. mpMRI-invisible tumors exhibited molecular, cellular, and structural characteristics more akin to normal prostate tissue, which may render them undetectable by imaging. A stroma-associated gene signature, a mpMRI-invisible tumor feature, correlated with better PCa clinical outcomes.

Download Full-text

Magnetic resonance fingerprinting in prostate cancer before and after contrast enhancement

British Journal of Radiology ◽

10.1259/bjr.20210479 ◽

2021 ◽

pp. 20210479

Author(s):

Young Sub Lee ◽

Moon Hyung Choi ◽

Young Joon Lee ◽

Dongyeob Han ◽

Dong-Hyun Kim

Keyword(s):

Prostate Cancer ◽

Magnetic Resonance ◽

Prostate Gland ◽

Prostate Tissue ◽

Normal Prostate ◽

Adc Value ◽

Contrast Enhanced ◽

Normal Prostate Tissue ◽

Adc Values ◽

T1 And T2

Objectives: To assess the apparent diffusion coefficient (ADC) values and the T1 and T2 values derived from nonenhanced (NE) and contrast-enhanced (CE) magnetic resonance fingerprinting (MRF) in the prostate gland and to evaluate differences in values among prostate cancer, the normal peripheral zone (PZ) and the normal transition zone (TZ). Methods: Fifty-seven patients (median age, 73 years; range, 48–86) with prostate cancer who underwent multiparametric MRI including NE and CE MRF were included in this study. T1 and T2 values were extracted from NE and CE MRF, respectively. Five quantitative values (the ADC, NE T1, NE T2, CE T1 and CE T2 values) were measured in three areas: prostate cancer, PZ and TZ. We compared the values among the three areas and evaluated the differences between NE MRF and CE MRF values. Results: ADC values and MRF-derived values were significantly higher in PZ than prostate cancer or TZ (p < 0.001). TZ had a significantly lower CE T1 but significantly higher values of the other variables than prostate cancer (p < 0.001). The T1 values in all three areas and the T2 values in prostate cancer and TZ were significantly lower on CE MRF than on NE MRF (p < 0.001). Conclusions: Quantitative analysis of NE and CE MRI can be conducted by using the MRF technique. The ADC value and the T1 and T2 values from CE MRF and NE MRF were found to be significantly different between prostate cancer and normal prostate tissue. Advances in knowledge The T1 and T2 values from contrast-enhanced MR fingerprinting are significantly different between prostate cancer and normal prostate tissue.

Download Full-text