Benign Prostatic Hyperplasia Tissue Research Articles

Activation of the cGMP/PKG/ERK signaling pathway associated with PDE5Is inhibits fibroblast activation by downregulating autophagy in early progressive benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is one of the most prevalent diseases affecting aging males. However, approximately, 8% of the BPH patients under 50-year-old experience remarkably early progression, for reasons that remain elusive. Among the various factors implicated in promoting BPH advancement, the activation of fibroblasts and autophagy hold particular importance. Our research endeavors to explore the mechanisms behind the accelerated progression in these patients. Immunohistochemistry and immunofluorescence were performed to detect the expression levels of LC3, p62, PDE5, and α-SMA in diverse BPH tissues and prostate stromal cells. The autophagy activator rapamycin, the autophagy suppressor chloroquine, and siRNA transfection were used to identify the impact of autophagy on fibroblast activation. Prostatic stromal fibroblasts in early progressive BPH tissues displayed activation of autophagy with an upregulation of LC3 and a concurrent downregulation of p62. After starvation or rapamycin treatment to a heightened level of autophagy, fibroblasts exhibited activation. Conversely, chloroquine treatment and ATG-7-knockdown effectively suppressed the level of autophagy and fibroblast activation. High expression of PDE5 was found in early progressive BPH stromal cells. The administration of PDE5 inhibitors (PDE5Is) hindered fibroblast activation through suppressing autophagy by inhibiting the ERK signaling pathway. Our findings suggest that autophagy plays a pivotal role in promoting BPH progression through fibroblast activation, while PDE5Is effectively suppress autophagy and fibroblast activation via the ERK signaling pathway. Nevertheless, further investigations are warranted to comprehensively elucidate the role of autophagy in BPH progression.

Aberrant activation of TGF-β/ROCK1 enhances stemness during prostatic stromal hyperplasia

Benign prostatic hyperplasia (BPH) is a multifactorial disease in which abnormal growth factor activation and embryonic reawakening are considered important factors. Here we demonstrated that the aberrant activation of transforming growth factor β (TGF-β)/Rho kinase 1 (ROCK1) increased the stemness of BPH tissue by recruiting mesenchymal stem cells (MSCs), indicating the important role of embryonic reawakening in BPH. When TGF-β/ROCK1 is abnormally activated, MSCs are recruited and differentiate into fibroblasts/myofibroblasts, leading to prostate stromal hyperplasia. Further research showed that inhibition of ROCK1 activation suppressed MSC migration and their potential for stromal differentiation. Collectively, our findings suggest that abnormal activation of TGF-β/ROCK1 regulates stem cell lineage specificity, and the small molecule inhibitor GSK269962A could target ROCK1 and may be a potential treatment for BPH.Graphical

Integrating spatial transcriptomics and single-cell RNA-sequencing reveals the alterations in epithelial cells during nodular formation in benign prostatic hyperplasia

ObjectiveProliferative nodular formation represents a characteristic pathological feature of benign prostatic hyperplasia (BPH) and serves as the primary cause for prostate volume enlargement and consequent lower urinary tract symptoms (LUTS). Its specific mechanism is largely unknown, although several cellular processes have been reported to be involved in BPH initiation and development and highlighted the crucial role of epithelial cells in proliferative nodular formation. However, the technological limitations hinder the in vivo investigation of BPH patients.MethodsThe robust cell type decomposition (RCTD) method was employed to integrate spatial transcriptomics and single cell RNA sequencing profiles, enabling the elucidation of epithelial cell alterations during nodular formation. Immunofluorescent and immunohistochemical staining was performed for verification.ResultsThe alterations of epithelial cells during the formation of nodules in BPH was observed, and a distinct subgroup of basal epithelial (BE) cells, referred to as BE5, was identified to play a crucial role in driving this progression through the hypoxia-induced epithelial-mesenchymal transition (EMT) signaling pathway. BE5 served as both the initiating cell during nodular formation and the transitional cell during the transformation from luminal epithelial (LE) to BE cells. A distinguishing characteristic of the BE5 cell subgroup in patients with BPH was its heightened hypoxia and upregulated expression of FOS. Histological verification results confirmed a significant association between c-Fos expression and key biological processes such as hypoxia and cell proliferation, as well as the close relationship between hypoxia and EMT in BPH tissues. Furthermore, a strong link between c-Fos expression and the progression of BPH was also been validated. Additionally, notable functional differences were observed in glandular and stromal nodules regarding BE5 cells, with BE5 in glandular nodules exhibiting enhanced capacities for EMT and cell proliferation characterized by club-like cell markers.ConclusionsThis study elucidated the comprehensive landscape of epithelial cells during in vivo nodular formation in patients, thereby offering novel insights into the initiation and progression of BPH.

Enhancing surgical outcomes: accurate identification and removal of prostate cancer with B7-H3-targeted NIR-II molecular imaging.

One of the main reasons for prostate cancer (PCa) recurrence is the difficulty in identifying and removing cancerous lesions during surgery. Accurately localizing and excising cancerous tissue remains a significant challenge. The second near-infrared window (NIR-II, 1000-1700nm) fluorescence offers enhanced resolution, a high signal-to-noise ratio, and the potential for deeper tissue penetration. However, this technology is not currently employed for intraoperative imaging of PCa. This study aims to construct a new NIR-II probe targeting B7-H3 (AbB7-H3-800CW) for accurate intraoperative identification and resection of PCa. Based on the differential expression of B7-H3 in PCa, we designed a novel imaging probe to accurately identify and guide the resection of preclinical PCa models and ex vivo human PCa tissues using NIR-II fluorescence imaging technology. Analyzing tissue samples from 60 clinical cases of PCa, along with benign prostatic hyperplasia and normal prostate tissue from 22 cases, we observed a significant difference in B7-H3 protein expression levels (P < 0.001). Subcutaneous and orthotopic mouse models of PCa were imaged using NIR-II fluorescence after AbB7-H3-800CW injection, showing promising results with successful tumor targeting and high-contrast images achieved within 24-48h post-injection. The imaging also enabled the detection of occult PCa lesions approximately 1mm in diameter. In addition, imaging analysis of human PCa and adjacent tissues using AbB7-H3-800CW incubation revealed that cancer tissues exhibited a significantly higher fluorescence intensity than adjacent tissues (P < 0.05), which was conducive to the evaluation of tumor resection margin in vitro. The findings revealed that B7-H3 was a compelling imaging target for PCa. The AbB7-H3-800CW molecular imaging probe is capable of accurately identifying PCa lesions and guiding their removal. This approach can potentially reduce the rate of surgical margins under NIR-II fluorescence guidance.

Overexpression of Transmembrane Phosphatase with Tensin homology (TPTE) in prostate cancer is clinically significant, suggesting its potential as a valuable biomarker

PurposeCancer testis antigens (CTAs) are a family of proteins typically expressed in male testicles but overexpressed in various cancer cell types. Transmembrane Phosphatase with Tensin homology (TPTE) is expressed only in the testis of healthy individuals and is a member of the family of CTAs. The current study, for the first time, examined the significance of TPTE expression in prostate cancer (PCa) tissues by generating a novel antibody marker targeting TPTE protein.MethodsPolyclonal antibodies were prepared for TPTE-p1 and TPTE-p2 peptides, which are derived from the extracellular domains of TPTE. Anti-TPTE-p2 antibody was then used to study the extent and pattern of TPTE expression in 102 PCa and 48 benign prostatic hyperplasia (BPH) tissue samples by immunohistochemistry. The viability of cancer cell lines (PC-3 and MCF-7 cells) was also evaluated in the presence of anti-TPTE-p2 antibody using the MTT test.ResultsThe immunohistochemical analysis demonstrated a significant increase in cytoplasmic and membrane TPTE expression in the PCa samples compared to the BPH group (both P < 0.0001). Cytoplasmic TPTE expression was positively correlated with Gleason score and PSA levels (P = 0.03 and P = 0.001, respectively). Significant correlations were identified between the levels of PSA and perineural invasion and the membrane expression (P = 0.01, P = 0.04, respectively). Moreover, anti-TPTE-p2 antibody inhibited PC-3 and MCF-7 cells proliferation compared to the control group for 24 h (P < 0.001 and P = 0.001, respectively) as well as for 48 h (P = 0.001 and P = 0.001, respectively).ConclusionOur findings indicate that increased TPTE expression is associated with progression of disease. The ability of anti-TPTE-p2 antibody to recognize and target the TPTE protein makes it a potential biomarker to assess and/or target the PCa.

Microbiome analysis reveals the inducing effect of Pseudomonas on prostatic hyperplasia via activating NF-κB signalling

ABSTRACT Benign prostatic hyperplasia (BPH) is a prevalent disease among middle-aged and elderly males, but its pathogenesis remains unclear. Dysbiosis of the microbiome is increasingly recognized as a significant factor in various human diseases. Prostate tissue also contains a unique microbiome, and its dysbiosis has been proposed to contribute to prostate diseases. Here, we obtained prostate tissues and preoperative catheterized urine from 24 BPH individuals, and 8 normal prostate samples as controls, which followed strict aseptic measures. Using metagenomic next-generation sequencing (mNGS), we found the disparities in the microbiome composition between normal and BPH tissues, with Pseudomonas significantly enriched in BPH tissues, as confirmed by fluorescence in situ hybridization (FISH). Additionally, we showed that the prostate microbiome differed from the urine microbiome. In vitro experiments revealed that lipopolysaccharide (LPS) of Pseudomonas activated NF-κB signalling, leading to inflammation, proliferation, and EMT processes, while inhibiting apoptosis in prostatic cells. Overall, our research determines the presence of microbiome dysbiosis in BPH, and suggests that Pseudomonas, as the dominant microflora, may promote the progression of BPH through LPS activation of NF-κB signalling.

Transcriptomic analysis of benign prostatic hyperplasia identifies critical pathways in prostatic overgrowth and 5-alpha reductase inhibitor resistance.

The medical therapy of prostatic symptoms (MTOPS) trial randomized men with symptoms of benign prostatic hyperplasia (BPH) and followed response of treatment with a 5α-reductase inhibitor (5ARI), an alpha-adrenergic receptor antagonist (α-blocker), the combination of 5ARI and α-blocker or no medical therapy (none). Medical therapy reduced risk of clinical progression by 66% but the reasons for nonresponse or loss of therapeutic response in some patients remains unresolved. Our previous work showed that prostatic glucocorticoid levels are increased in 5ARI-treated patients and that glucocorticoids can increased branching of prostate epithelia in vitro. To understand the transcriptomic changes associated with 5ARI treatment, we performed bulk RNA sequencing of BPH and control samples from patients who received 5ARI versus those that did not. Deconvolution analysis was performed to estimate cellular composition. Bulk RNA sequencing was also performed on control versus glucocorticoid-treated prostate epithelia in 3D culture to determine underlying transcriptomic changes associated with branching morphogenesis. Surgical BPH (S-BPH) tissue was defined as benign prostatic tissue collected from the transition zone (TZ) of patients who failed medical therapy while control tissue termed Incidental BPH (I-BPH) was obtained from the TZ of men undergoing radical prostatectomy for low-volume/grade prostatic adenocarcinoma confined to the peripheral zone. S-BPH patients were divided into four subgroups: men on no medical therapy (none: n = 7), α-blocker alone (n = 10), 5ARI alone (n = 6) or combination therapy (α-blocker and 5ARI: n = 7). Control I-BPH tissue was from men on no medical therapy (none: n = 8) or on α-blocker (n = 6). A human prostatic cell line in 3D culture that buds and branches was used to identify genes involved in early prostatic growth. Snap-frozen prostatic tissue taken at the time of surgery and 3D organoids were used for RNA-seq analysis. Bulk RNAseq data were deconvoluted using CIBERSORTx. Differentially expressed genes (DEG) that were statistically significant among S-BPH, I-BPH, and during budding and branching of organoids were used for pathway analysis. Transcriptomic analysis between S-BPH (n = 30) and I-BPH (n = 14) using a twofold cutoff (p < 0.05) identified 377 DEG (termed BPH377) and a cutoff < 0.05 identified 3377 DEG (termed BPH3377). Within the S-BPH, the subgroups none and α-blocker were compared to patients on 5ARI to reveal 361 DEG (termed 5ARI361) that were significantly changed. Deconvolution analysis of bulk RNA seq data with a human prostate single cell data set demonstrated increased levels of mast cells, NK cells, interstitial fibroblasts, and prostate luminal cells in S-BPH versus I-BPH. Glucocorticoid (GC)-induced budding and branching of benign prostatic cells in 3D culture was compared to control organoids to identify early events in prostatic morphogenesis. GC induced 369 DEG (termed GC359) in 3D culture. STRING analysis divided the large datasets into 20-80 genes centered around a hub. In general, biological processes induced in BPH supported growth and differentiation such as chromatin modification and DNA repair, transcription, cytoskeleton, mitochondrial electron transport, ubiquitination, protein folding, and cholesterol synthesis. Identified signaling pathways were pooled to create a list of DEG that fell into seven hubs/clusters. The hub gene centrality was used to name the network including AP-1, interleukin (IL)-6, NOTCH1 and NOTCH3, NEO1, IL-13, and HDAC/KDM. All hubs showed connections to inflammation, chromatin structure, and development. The same approach was applied to 5ARI361 giving multiple networks, but the EGF and sonic hedgehog (SHH) hub was of particular interest as a developmental pathway. The BPH3377, 5ARI363, and GC359 lists were compared and 67 significantly changed DEG were identified. Common genes to the 3D culture included an IL-6 hub that connected to genes identified in BPH hubs that defined AP1, IL-6, NOTCH, NEO1, IL-13, and HDAC/KDM. Reduction analysis of BPH and 3D organoid culture uncovered networks previously identified in prostatic development as being reinitiated in BPH. Identification of these pathways provides insight into the failure of medical therapy for BPH and new therapeutic targets for BPH/LUTS.

STEAP4 modulates cell proliferation and oxidative stress in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a quite common chronic disease plagued elderly men and its etiology remains unclear. It was reported that the six-transmembrane epithelial antigen of prostate 4 (STEAP4) could modulate cell proliferation/apoptosis ratio and oxidative stress in cancers. Our current study aimed to explore the expression, biological function, and underlying mechanism of STEAP4 in BPH progress. Human prostate tissues and cell lines were utilized. qRT-PCR and immunofluorescence staining were employed. STEAP4 knockdown (STEAP4-KD) or STEAP4 overexpression (STEAP4-OE) cell models were established. Cell proliferation, cell cycle, apoptosis, and reactive oxygen species (ROS) were determined by cell counting kit-8 (CCK-8) assay and flow cytometry. Apoptosis-related proteins and antioxidant enzymes were identified by Western Blot. In addition, the epithelial-mesenchymal transition (EMT) process and fibrosis biomarker (collagen I and α-SMA) were analyzed. It was indicated that STEAP4 was mainly located in the prostate epithelium and upregulated in BPH tissues. STEAP4 deficiency induced apoptosis and inhibited cell survival, but had no effect on the cell cycle, fibrosis, and EMT process. In addition, ROS changes were observed in the STEAP4-KD model. Consistently, overproduction of STEAP4 suppressed apoptosis and promoted cell proliferation, as well as facilitated ROS production. We further examined AKT / mTOR, p38MAPK / p-p38MAPK, and WNT/ β-Catenin signaling pathway and demonstrated that STEAP4 regulated the proliferation and apoptosis of prostate cells through AKT / mTOR signaling, rather than p38MAPK / p-p38MAPK and WNT/ β-Catenin pathways. Furthermore, activating AKT / mTOR signaling with SC79 significantly reversed apoptosis triggered by STEAP4 deficiency, whereas suppressing AKT / mTOR signaling with MK2206 reduced the increase of cell viability triggered by STEAP4 overproduction. Our original data demonstrated that STEAP4 is crucial in the onset and progression of prostate hyperplasia and may become a new target for the treatment of BPH.

Spatial architectures of somatic mutations in normal prostate, benign prostatic hyperplasia and coexisting prostate cancer

This study aimed to identify somatic mutations in nontumor cells (NSMs) in normal prostate and benign prostatic hyperplasia (BPH) and to determine their relatedness to prostate cancer (PCA). From 22 PCA patients, two prostates were sampled for 3-dimensional mapping (50 normal, 46 BPH and 1 PCA samples), and 20 prostates were trio-sampled (two normal or BPH samples and one PCA sample) and analyzed by whole-genome sequencing. Normal and BPH tissues harbored several driver NSMs and copy number alterations (CNAs), including in FOXA1, but the variations exhibited low incidence, rare recurrence, and rare overlap with PCAs. CNAs, structural variants, and mutation signatures were similar between normal and BPH samples, while BPHs harbored a higher mutation burden, shorter telomere length, larger clone size, and more private NSMs than normal prostates. We identified peripheral-zonal dominance and right-side asymmetry in NSMs, but the asymmetry was heterogeneous between samples. In one normal prostate, private oncogenic RAS-signaling NSMs were detected, suggesting convergence in clonal maintenance. Early embryonic mutations exhibited two distinct distributions, characterized as layered and mixed patterns. Our study identified that the BPH genome differed from the normal prostate genome but was still closer to the normal genome than to the PCA genome, suggesting that BPH might be more related to aging or environmental stress than to tumorigenic processes.

28S rRNA-Derived Fragments Represent an Independent Molecular Predictor of Short-Term Relapse in Prostate Cancer.

Prostate cancer (PCa) is a global health concern, being a leading cause of cancer-related mortality among males. Early detection and accurate prognosis are crucial for effective management. This study delves into the diagnostic and prognostic potential of 28S rRNA-derived fragments (rRFs) in PCa. Total RNA extracted from 89 PCa and 53 benign prostate hyperplasia (BPH) tissue specimens. After 3'-end polyadenylation, we performed reverse transcription to create first-strand cDNA. Using an in-house quantitative real-time PCR (qPCR) assay, we quantified 28S rRF levels. Post-treatment biochemical relapse served as the clinical endpoint event for survival analysis, which we validated internally through bootstrap analysis. Our results revealed downregulated 28S rRF levels in PCa compared to BPH patients. Additionally, we observed a significant positive correlation between 28S rRF levels and higher Gleason scores and tumor stages. Furthermore, PCa patients with elevated 28S rRF expression had a significantly higher risk of post-treatment disease relapse independently of clinicopathological data. In conclusion, our study demonstrates, for the first time, the prognostic value of 28S rRF in prostate adenocarcinoma. Elevated 28S rRF levels independently predict short-term PCa relapse and enhance risk stratification. This establishes 28S rRF as a potential novel molecular marker for PCa prognosis.

Identification of differentially expressed circRNAs in prostate cancer of different clinical stages by RNA sequencing

Circular RNAs (circRNAs) are linked to cancer, but it's still not clear what role they play in prostatic cancer. Through high-throughput sequencing, the goal of this study was to compare how circRNAs are expressed at different stages of prostate cancer. 12 patients attending the Department of Urology at the Second Affiliated Hospital of Nanchang University between June 2020 and October 2021 were used for RNA sequencing, and 14 patients were used for real-time fluorescent quantitative PCR (qRT-PCR). The expression profiles of prostate cancer circRNAs were constructed by sequencing with the help of next-generation high-throughput sequencing technology, and the differentially expressed circRNAs were analyzed by targeting microRNA (miRNA) loci and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the genes from which circRNAs originated. Finally, the expression of target circRNAs in two prostate tissues was verified by qRT-PCR. Following high-throughput sequencing, 13,047 circRNAs were identified, and 605 circRNAs with significant differential expression were identified, of which 361 circRNAs were up-regulated, and 244 circRNAs were down-regulated. Analysis of circRNA-originated genes using GO and the KEGG enrichment analysis showed that circRNA host genes can regulate and influence multiple signaling pathways in prostate cancer with important biological functions. And the circRNA–miRNA network was constructed. The highest number of differentially expressed circRNA-binding miRNAs were: hsa_circ_000 7582 (52), hsa_circ_000 6198 (37), hsa_circ_000 6759 (28), hsa_circ_000 5675 (25), and hsa_circ_000 2172 (22). Moreover, we further screened out the circRNA (hsa_circ_0005692) that was significantly differentially expressed and common to all groups and verified by qRT-PCR that the expression of the target circRNA (hsa_circ_0005692) was significantly downregulated in prostate cancer compared with benign prostatic hyperplasia (BPH) tissues.

The activated complement pathway in the fibrous process of benign prostatic hyperplasia.

To elucidate the changes in activated complement pathway in the fibrous process of benign prostatic hyperplasia (BPH), we analyzed the correlation between complement component expression and histological types of fibrosis using human BPH tissue. Fifty-six histological BPH patients who underwent prostate needle biopsy at our institution (mean age 68.6 ± 6.5 years), divided into two histological groups, fibromuscular and fibrous, were compared. Inflammatory cell infiltration in BPH tissue was evaluated by immunohistochemical staining using CD45, with complement expression analysis performed using C3, factor B, and C5b-9 antibody, and the occupancy ratio of the stained region was calculated. Further, correlation between the histological types of fibrous components in BPH tissue and lower urinary tract symptoms questionnaires was analyzed. Twenty-seven (48.2%) and 29 (51.8%) cases were classified in the fibromuscular and fibrous groups, respectively. The proportion of CD45-positive cells in BPH tissue was significantly higher in the fibromuscular group. In complement component analysis, factor B did not significantly differ between groups, while C3 (fibromuscular group; 10.7 ± 8.2%, fibrous group; 16.4 ± 12.7%) and C5b-9 (fibromuscular group; 15.9 ± 6.2%, fibrous group; 17.6 ± 9.2%) were significantly higher in the fibrous group (p = 0.04, p = 0.04, respectively). International Prostate Symptom Score Q5 subscore, indicating slow stream, was significantly higher in the fibrous group (p = 0.04). In fibrous BPH with abundant fibrosis, the late complement pathway in addition to alternative pathway was activated compared to fibromuscular BPH. These results suggested that the alternative and late complement pathways were involved in the histological fibrous process of BPH.

BPH-related False Positive of PSMA-PET in the Diagnosis of Prostate Cancer: the Achilles' Heel of Biopsy-free Radical Prostatectomy?

Radical prostatectomy is one of the primary treatments for localized clinically significant prostate cancer. Generally, its application is based on prior biopsy. PSMA-PET is considered promising in biopsy-free radical prostatectomy. The expression of PSMA in benign prostatic hyperplasia tissue and corresponding positive reaction are crucial concerns for no biopsy strategy. Currently, no study has explored the benign prostatic hyperplasia-related false positive of PSMA-PET in the detection of prostate cancer. Furthermore, the influence of SUVmax and PI-RADS on biopsy-free radical prostatectomy is also poorly characterized. A retrospective study was conducted on patients who received PSMA-PET because of clinical suspicion of prostate cancer and were confirmed to be benign prostatic hyperplasia or prostate cancer. The receiver operating characteristic curve was generated for SUVmax. Results of interest were the false positive rate of PSMA-PET and the efficacy of SUVmax or mpMRI in excluding false positives. The benign prostatic hyperplasia-related false positive rate of PSMA-PET in detecting prostate cancer was 30%. SUVmax could effectively exclude benign prostatic hyperplasia and grade group 1 patients with an area under the curve of 0.86, the optimal SUVmax cutoff value with 100% specificity was 15, with a sensitivity of 41%. Notably, the sensitivity and specificity of stringent PET score and PI-RADS criteria (both ≥ 4) in diagnosing clinically significant prostate cancer were 49% and 100%, respectively. Our findings revealed benign prostatic hyperplasia-related false positive rate of PSMA-PET and provided a preliminary reference in biopsy-free radical prostatectomy.

Therapeutic potential of pomegranate juice-derived nanovesicles in nude mouse benign prostatic hyperplasia (BPH) xenograft model

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms affect a large percentage of the male population and places a substantial burden on the world health system. Current therapies include 5-alpha reductase inhibitors and alpha-blockers that are only partially effective and pose a huge economic burden, emphasizing the urgent need for effective, economical therapies. We isolated nanovesicles from pomegranate juice (Punica Granatum) (referred to as ‘POM-NVs’) and report to our knowledge for the first time, that these vesicles possess therapeutic potential against BPH. Following extensive characterization of POM-NVs, we tested their therapeutic potential in vitro using BPH1 cell line and identified a potential anti-proliferative and pro-apoptotic effect. We further tested these vesicles using a clinically relevant xenograft mouse BPH model derived from human BPH tissues. Remarkably, POM-NVs could reverse the BPH phenotype conferred by TGF-β mediated signaling and induced epithelial-to-mesenchymal (EMT) reversal, leading to the restoration of prostate epithelial states in vivo and in vitro. Furthermore, these vesicles attenuated bone morphogenic protein 5 (BMP5) signaling, a cardinal alteration that is instrumental in driving BPH. Considering the large incidences of BPH and its associated economic burdens, our study has important implications and can potentially improve the clinical management of BPH.

Mechanism of Androgen-Independent Stromal Proliferation in Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH) is a chronic proliferative disease showing stromal-dominant proliferation. However, the detailed proliferation mechanism has remained unclear. Although aging and androgen have been reported as definitive risk factors for BPH, recent studies have focused on the involvement of androgen-independent factors. Androgen-independent factors include ischemia, oxidative stress, metabolic syndrome, infection, autoimmune reactions, and inflammation, with inflammation in BPH tissues playing a central role in the BPH proliferative process. Inflammation in BPH tissues by various factors finally leads to tissue remodeling and stromal proliferation through the wound healing process of the prostate. To elucidate the proliferative mechanism of BPH, a study using whole-genome gene expression analysis in a stromal-dominant BPH rat model was performed and showed that immune response-related pathways and complement classical pathways are activated. Furthermore, expression analysis using this BPH rat model showed that the autoimmune reaction triggered complement pathway activation in the proliferative process of BPH. BPH is a multifactorial disease, and understanding the role of androgen-independent factors including immune responses contributes to elucidating the pathogenesis of BPH. Androgen-independent factors may lead to new therapeutic targets for BPH, and further development of this research is expected.

Prostrate malignant tumor and benign prostatic hyperplasia microenvironments in black African men: Limited infiltration of CD8+ T lymphocytes, NK-cells, and high frequency of CD73+ stromal cells.

Anti-cancerous immunology has yet to be investigated in the African black population, despite being the dawn of precision medicine. Here we investigated the tumor microenvironment of prostate cancer and benign prostatic hyperplasia (BPH) in black Africans. Through immunohistochemistry analysis of prostate cancer and BPH patients' biopsies, we investigated the expression and distribution of CD73, CCD8 T-lymphocytes, and natural killer cells. In addition, we looked at tumor-infiltrating features CD8 T-lymphocytes and natural killer cells. We show for the first time in black Africans a high expression of CD73 in epithelial-stromal cells and virtually no infiltration of CD8 T lymphocytes and natural killer cells in the tumoral area. In addition, CD73 was seven (7) times more likely to be expressed in prostate cancer stromal tissues than in benign prostatic hyperplasia tissues (odds ratio = 7.2; χ2 = 21; p < .0001). In addition, PSA concentration was significantly higher in prostate cancer patients than in BPH patients (p < .001). Also, the PSA-based ROC. analysis showed an area under the curve of 0.87 (p < .0001). CD73 expression is more likely expressed in prostate cancer stromal tissues than in benign prostatic hyperplasia tissues. The features of prostate cancer in Black Africans suggest CD73 expression as a possible target for immunotherapy in this population.

Decellularization and Recellularization of Natural, Benign Prostatic Hyperplasia and Malignant Human Prostatic Tissues: Role of Extracellular Matrix Behavior on Development of Prostate Cancer

Decellularization and Recellularization of Natural, Benign Prostatic Hyperplasia and Malignant Human Prostatic Tissues: Role of Extracellular Matrix Behavior on Development of Prostate Cancer

HP1α promotes the progression of prostate cancer.

Patients who have been diagnosed with prostate cancer (PCa) typically have a dismal outlook and few therapeutic choices available to them, because the precise pathogenesis of the disease is not yet fully understood. The presence of HP1α, also known as the heterochromatin protein 1α, is required for the creation of higher-order chromatin structures. However, little is known about HP1α that serves roles in the pathogenesis of PCa. The primary purpose of our research was to investigate alterations in the levels of HP1α expression and to plan a series of tests to validate the function of HP1α in PCa. Information on HP1α expression in PCa and benign prostatic hyperplasia (BPH) tissues were gathered using the Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. RT-qPCR, western blotting, and immunohistochemistry (IHC) were used to assess HP1α mRNA and protein expression in several human PCa tissues and cell lines. The CCK8 assay, clone formation assay, and transwell assay were used to examine biological activities including cell proliferation, migration, and invasion. The expression of proteins connected to apoptosis and the epithelial-mesenchymal transition (EMT) was examined using Western blot. The tumorigenic effect of HP1α was also verified by in vivo experiments. HP1α expression was much higher in PCa than in BPH tissues and cells, and was positively correlated with the Gleason score of PCa. In vitro experiments showed that HP1α knockdown could inhibit the ability of proliferation, invasion, and migration of PC3 and LNCaP cells, and promote cell apoptosis and EMT. In vivo experiments showed that HP1α knockdown inhibited tumorigenesis in mice. Our findings indicate that HP1α expression promotes PCa development and might be a novel therapeutic target for the diagnosis or treatment of PCa.

PD38-02 BPH-RELATED FALSE POSITIVE OF 68 GA-PSMA PET/CT IN THE DIAGNOSIS OF PROSTATE CANCER: THE ACHILLES' HEEL OF BIOPSY-FREE RADICAL PROSTATECTOMY?

You have accessJournal of UrologyCME1 Apr 2023PD38-02 BPH-RELATED FALSE POSITIVE OF 68GA-PSMA PET/CT IN THE DIAGNOSIS OF PROSTATE CANCER: THE ACHILLES' HEEL OF BIOPSY-FREE RADICAL PROSTATECTOMY? Wei Tang, Yongxiang Tang, Lin Qi, Ye Zhang, Guyu Tang, Xiaomei Gao, Shuo Hu, and Yi Cai Wei TangWei Tang More articles by this author , Yongxiang TangYongxiang Tang More articles by this author , Lin QiLin Qi More articles by this author , Ye ZhangYe Zhang More articles by this author , Guyu TangGuyu Tang More articles by this author , Xiaomei GaoXiaomei Gao More articles by this author , Shuo HuShuo Hu More articles by this author , and Yi CaiYi Cai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003336.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical prostatectomy (RP) is the primary treatment for localized clinically significant prostate cancer (csPCa). However, its application is generally based on prior pathological diagnosis. 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) is considered promising in biopsy-free RP. Notably, inadequate specific or positive predictive value of imaging diagnosis strategy could become the Achilles’ Heel of biopsy-free RP. For 68Ga-PSMA PET/CT, the expression of PSMA in benign prostatic hyperplasia (BPH) tissue and its related positive reaction, which can reduce the specificity of diagnosis, are important concerns affecting the imaging diagnosis of PCa as well as the feasibility of biopsy-free RP. No study has explored the BPH-related false positive of 68Ga-PSMA PET/CT in the detection of PCa. Furthermore, the influence of maximum standardized uptake value (SUVmax) on biopsy-free RP is also poorly characterized. METHODS: A retrospective descriptive observational study was conducted. Patients who received 68Ga-PSMA PET/CT because of clinical suspicion of PCa based on elevated prostate-specific antigen ( >4 ng/ml) or abnormal digital rectal examination and subsequently were confirmed to be BPH or PCa by systematic biopsy or targeted biopsy (TB) were included. The receiver operating characteristic curve was generated for SUVmax values, from which the area under the curve (AUC) and the Youden index was calculated. Sensitivity and specificity were calculated based on the cutoffs. RESULTS: 89 BPH and 94 PCa patients were included. 27 of the 89 BPH cases were considered 68Ga-PSMA PET/CT positive, all dominant lesions were confirmed to be BPH tissue through TB, and thus, were regarded as BPH-related false positive. The rate was 30.3%. SUVmax could effectively distinguish BPH and grade group (GG) one patients with an AUC of 0.8562 and could potentially benefit biopsy-free RP by avoid BPH-related misdiagnosis and GG one-related overtreatment. The optimal SUVmax cutoff value was 9.750 with a sensitivity of 64.71% and a specificity of 97.22%. Given the pivotal role of specificity in biopsy-free RP, we investigated the optimal SUVmax cutoff under when the specificity was 100%. The result was 14.60, with a sensitivity of 41.18% and a specificity of 100%. CONCLUSIONS: Our results revealed, for the first time, the BPH-related false positive rate of 68Ga-PSMA PET/CT in the primary diagnosis of PCa. Using SUVmax values in biopsy-free RP can effectively exclude both BPH and GG one patients. Source of Funding: This research was supported by the key Research and Development program of Hunan Province (2021SK2014), the Science and Technology Innovation Team Talent Project of Hunan Province (2021 RC4056), the National Natural Science Foundation of China (82272907, 81974397, 81572524, 91859207, 81771873), the National Natural Science Foundation of Hunan Province (2020JJ5882) and the clinical research foundation of the National Clinical Research Center for Geriatric Diseases (XIANGYA) (2020LNJJ01) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e993 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wei Tang More articles by this author Yongxiang Tang More articles by this author Lin Qi More articles by this author Ye Zhang More articles by this author Guyu Tang More articles by this author Xiaomei Gao More articles by this author Shuo Hu More articles by this author Yi Cai More articles by this author Expand All Advertisement PDF downloadLoading ...

Expression and functional activity of myosin II in hyperplastic prostates of varying volumes

Prostate volume (PV) differs dramatically among benign prostatic hyperplasia (BPH) patients. Estimation of PV is important to guide the most appropriate pharmacologic or interventional treatment approach. However, the underlying pathophysiological mechanisms for the differences in PV remain unknown. We recently found that the myosin II system might participate in the etiology and development of BPH via static and dynamic factors. Our present study aims to explore the expression and functional activities of myosin II isoforms including smooth muscle (SM) myosin II (SMM II) and non-muscle myosin II (NMM II) in hyperplastic prostates with varied PV. Human hyperplastic prostates and the testosterone-induced rat BPH model were employed for this study. Hematoxylin and Eosin (H&E), Masson's trichrome, immunohistochemical staining, in vitro organ bath, RT-polymerase chain reaction (PCR) and Western-blotting were performed. Also, a BPH tissue microarray (TMA) was constructed to determine the correlations between myosin II isoforms with clinical parameters of BPH patients. With the increase of PV, the expression of NMMHC-A, NMMHC-C, SM-A and LC17b isoforms were increased, and the contractility of prostate smooth muscle was enhanced but force developed more slowly. Consistently, NMMHC-A, NMMHC-C, SM-A and LC17b were correlated positively with PV. Similar outcomes were also observed in the BPH rat model with different PVs. Alterations in the expression and function of myosin the II system may be involved in the pathophysiological mechanism of PV differences between BPH patients.