Advantage of whole-mount histopathology in prostate cancer: current applications and future prospects.

BACKGROUND: Whole-mount histopathology (WMH) has been a powerful tool to investigate the characteristics of prostate cancer. However, the latest advancement of WMH was yet under summarization. In this review, we offer a comprehensive exposition of current research utilizing WMH in diagnosing and treating prostate cancer (PCa), and summarize the clinical advantages of WMH and outlines potential on future prospects. METHODS: An extensive PubMed search was conducted until February 26, 2023, with the search term "prostate", "whole-mount", "large format histology", which was limited to the last 4 years. Publications included were restricted to those in English. Other papers were also cited to contribute a better understanding. RESULTS: WMH exhibits an enhanced legibility for pathologists, which improved the efficacy of pathologic examination and provide educational value. It simplifies the histopathological registration with medical images, which serves as a convincing reference standard for imaging indicator investigation and medical image-based artificial intelligence (AI). Additionally, WMH provides comprehensive histopathological information for tumor volume estimation, post-treatment evaluation, and provides direct pathological data for AI readers. It also offers complete spatial context for the location estimation of both intraprostatic and extraprostatic cancerous region. CONCLUSIONS: WMH provides unique benefits in several aspects of clinical diagnosis and treatment of PCa. The utilization of WMH technique facilitates the development and refinement of various clinical technologies. We believe that WMH will play an important role in future clinical applications.

The implications of single-cell RNA-seq analysis in prostate cancer: unraveling tumor heterogeneity, therapeutic implications and pathways towards personalized therapy.

In recent years, advancements in single-cell and spatial transcriptomics, which are highly regarded developments in the current era, particularly the emerging integration of single-cell and spatiotemporal transcriptomics, have enabled a detailed molecular comprehension of the complex regulation of cell fate. The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine. Currently, single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors. Starting from the perspective of RNA sequencing technology, this review outlined the significance of single-cell RNA sequencing (scRNA-seq) in prostate cancer research, encompassing preclinical medicine and clinical applications. We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies, as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis, treatment, and drug resistance characteristics of prostate cancer. These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer. Furthermore, we explore the potential clinical applications stemming from other single-cell technologies in this review, paving the way for future research in precision medicine.

Predictors of postoperative storage symptoms in male patients with lower urinary tract symptoms: A retrospective analysis of prostate surgery for benign prostatic enlargement.

OBJECTIVES: This study investigated the effects of prostate surgery on storage symptoms in male patients with lower urinary tract symptoms (LUTS) from benign prostatic enlargement (BPE). This study aimed to identify patient characteristics associated with improved, unchanged, and deteriorated post-surgical storage symptoms and to identify the risk factors for non-improvement or deterioration. METHODS: A retrospective analysis of 586 prostate surgeries performed between 2016 and 2022 at Yokosuka Kyosai Hospital was conducted on patients with LUTS and at least one storage symptom preoperatively. Patients with active urinary tract infection, prostate/bladder cancer, urethral strictures, or dementia were excluded. The study enrolled 230 patients and assessed storage symptoms using the International Prostate Symptom Score (IPSS). RESULTS: Overall, storage symptoms improved, remained unchanged, and deteriorated in 87.0%, 5.7%, and 7.4% of patients, respectively. The patients in the deteriorated group were significantly older, whereas those in the no-change group had smaller prostate volumes. Patient-reported outcome scores (IPSS, IPSS-QoL, and BII) were significantly higher in the improved group. The predictors of non-improvement included low IPSS storage score, cardiovascular disease, and diabetes mellitus. Predictors of deterioration included advanced age and low IPSS storage score. CONCLUSIONS: Patients with severe LUTS showed greater postoperative improvement in storage symptoms. A low IPSS storage score predicted non-improvement and deterioration. Advanced age, low IPSS storage score, and a history of cardiovascular disease and diabetes mellitus were identified as key predictors. Awareness of these factors may guide preoperative counseling and improve decision-making in prostate surgery, ensuring more personalized and effective treatment strategies.

Quantitative morphological analysis of age structural changes in prostate of experimental animals with ethanol poisoning.

OBJECTIVE: Aim: To find out the age remodeling of the structural components of the prostate gland at alcohol poisoning using quantitative morphological analysis. PATIENTS AND METHODS: Materials and Methods: The structure of the prostate gland of 4 white male rats groups were morphologically investigated. The 1 group included 30 control intact animals aged 8 months, the 2-nd group - 30 rats aged 24 months, the 3-rd group - 30 8-month-old animals with ethanol intoxication, and the 4-th group included 30 24-month-old rats with the specified simulated pathology. Ethanol intoxication was modeled by intragastric administration of 30% ethyl alcohol solution at a dose of 20 ml/kg once daily for 28 days. Rats were euthanized by bloodletting under general thiopental anesthesia 28 days after the beginning of the experiment. The area of glands, the height of glandular epithelial cells, the area of their nuclei and cytoplasm, the nuclear-cytoplasmic ratio in these cells and the stromal-parenchymal ratio in the organ were studied using light microscopy and were determined morphometrically. Morphometric parameters were processed statistically. RESULTS: Results: It was established that with age in the intact prostate of laboratory sexually mature white male rats, the area of glands, the height of glandular epitheliocytes, the area of their nuclei and cytoplasm, with the stability of nuclear-cytoplasmic ratios in the epithelial cells of the glands, significantly decreases, and the stromal-parenchymal ratio in the organ under study increases. Long-term ethanol poisoning leads to pronounced structural changes in the prostate, which is characterized by pronounced atrophy of the glandular epithelium, a decrease in the area of the glands, a decrease in the height of epithelial cells, a violation of nuclear-cytoplasmic relations in them, an increase in stromal-parenchymal ratio, and a prominent growth of the muscle-elastic stroma. The revealed structural changes of the studied components of the prostate dominated in 24-month-old experimental animals. CONCLUSION: Conclusions: Morphological analysis of the prostate gland established that morphometric and morphological changed significantly according to the age and were depend on the ethanol poisoning.

Primary mucinous adenocarcinoma of the urethra: A contemporary clinicopathologic analysis of 17 patients.

Mucinous adenocarcinoma of the urethra is rare. Here we performed a contemporary clinicopathologic analysis of this entity in both male and female patients. All cases with secondary tumors involving the urethra were excluded. Clinicopathologic parameters and follow up was obtained. Seventeen patients were included in the study, 9/17 (53 %) male and 8/17 (47 %) female. The mean patient age was 68 years (range: 53-88 years). The majority (11/17, 65 %) of patients were African American, with an even greater incidence (7/8, 87 %) in female patients. In male patients, prostatic urethra was the most common part of the urethra (6/9, 67 %) where the tumor arose from. Immunohistochemical stains were performed in 11/17 (65 %) tumors and were positive for CK20 (11/11, 100 %), CDX2 (11/12, 92 %), CK7 (8/9, 88 %), GATA3 (3/8, 37 %) and negative for NKX3.1, PSA, p63, PAX8, and Beta-Catenin. In resection specimens, tumors were categorized as pT2 (3/11, 27 %), pT3 (1/11, 9 %), and pT4 (7/11, 64 %). Lymph node status was categorized as pN0 (6/9, 67 %), pN1 (1/9, 11 %), and pN2 (2/9, 22 %). Available follow up data showed 7/13 (54 %) patients developed recurrence after surgical resection and chemotherapy, of which 3/7 (43 %) died of widespread metastatic disease. It is critical for pathologists and urologic oncologists to be aware of this entity in both male and female patients in view of potential diagnostic pitfalls, prognosis, and therapeutic implications.

EP300/CREBBP acetyltransferase inhibition limits steroid receptor and FOXA1 signaling in prostate cancer cells.

The androgen receptor (AR) is a primary target for treating prostate cancer (PCa), forming the bedrock of its clinical management. Despite their efficacy, resistance often hampers AR-targeted therapies, necessitating new strategies against therapy-resistant PCa. These resistances involve various mechanisms, including AR splice variant overexpression and altered activities of transcription factors like the glucocorticoid receptor (GR) and FOXA1. These factors rely on common coregulators, such as EP300/CREBBP, suggesting a rationale for coregulator-targeted therapies. Our study explores EP300/CREBBP acetyltransferase inhibition's impact on steroid receptor and FOXA1 signaling in PCa cells using genome-wide techniques. Results reveal that EP300/CREBBP inhibition significantly disrupts the AR-regulated transcriptome and receptor chromatin binding by reducing the AR-gene expression. Similarly, GR's regulated transcriptome and receptor binding were hindered, not linked to reduced GR expression but to diminished FOXA1 chromatin binding, restricting GR signaling. Overall, our findings highlight how EP300/CREBBP inhibition distinctively curtails oncogenic transcription factors' signaling, suggesting the potential of coregulatory-targeted therapies in PCa.

Value of magnetic resonance angiography before prostatic artery embolization for intervention planning.

Knowledge about anatomical details seems to facilitate the procedure and planning of prostatic artery embolization (PAE) in patients with symptomatic benign prostatic hyperplasia (BPS). The aim of our study was the pre-interventional visualization of the prostatic artery (PA) with MRA and the correlation of iliac elongation and bifurcation angles with technical success of PAE and technical parameters. MRA data of patients with PAE were analysed retrospectively regarding PA visibility, PA type, vessel elongation, and defined angles were correlated with intervention time, fluoroscopy time, dose area product (DAP), cumulative air kerma (CAK), contrast media (CM) dose and technical success of embolization. T-test, ANOVA, Pearson correlation, and Kruskal-Wallis test was applied for statistical analysis. Between April 2018 and March 2021, a total of 78 patients were included. MRA identified the PA origin in 126 of 147 cases (accuracy 86%). Vessel elongation affected time for catheterization of right PA (p = 0.02), fluoroscopy time (p = 0.05), and CM dose (p = 0.02) significantly. Moderate correlation was observed for iliac bifurcation angles with DAP (r = 0.30 left; r = 0.34 right; p = 0.01) and CAK (r = 0.32 left; r = 0.36 right; p = 0.01) on both sides. Comparing the first half and second half of patients, median intervention time (125 vs. 105 min.) and number of iliac CBCT could be reduced (p < 0.001). We conclude that MRA could depict exact pelvic artery configuration, identify PA origin, and might obviate iliac CBCT. Vessel elongation of pelvic arteries increased intervention time and contrast media dose while the PA origin had no significant influence on intervention time and/or technical success.

Evaluation of the effect of prostate diameters on erectile dysfunction in patients who underwent low-anterior resection.

OBJECTIVE: Male erectile dysfunction is an important complication of rectal surgery. In this research, the effect of prostate dimensions on the development of postoperative erectile dysfunction in patients diagnosed with mid-rectum adenocarcinoma who underwent low anterior resection (LAR) is examined. PATIENTS AND METHODS: Thirty-one male patients diagnosed as mid-rectal adenocancer were included. The International Index of Erectile Function (IIEF) questionnaire was used to determine the patients' pre and postoperative erectile dysfunction levels, and the level of relationship between the change in these IIEF scores and prostate measurements determined by computed tomography were evaluated. RESULTS: There were statistically significant differences between IIEF index score and anterior posterior (AP) and transverse (TR) measurements (p≤0.001; p≤0.001), but no statistically significant difference was found between craniocaudal (CC) measurement values (p=0.169). CONCLUSIONS: The risk of nerve injury will be higher in those with a small prostate transverse diameter. Intraoperative nerve monitoring should be recommended primarily in younger patient groups.

Comparison of urinary incontinence following three different prostate apex disconnection techniques in transurethral thulium laser prostatectomy.

OBJECTIVE: This study investigates the incidence of urinary incontinence following transurethral thulium laser prostatectomy with three different prostate apex disconnection techniques: semi-separation, pre-separation, and post-separation. The findings aim to provide references for clinical treatment. PATIENTS AND METHODS: A retrospective analysis was conducted on 74 patients treated with transurethral thulium laser prostatectomy for prostatic hyperplasia from April 2022 to March 2023. Complete clinical and follow-up data were available for 52 patients. Clinical and follow-up data were collected for these patients. A comparison was made of urinary incontinence following the three different types of prostate apex disconnection in transurethral thulium laser prostatectomy. RESULTS: In this study, the immediate postoperative urinary incontinence rate for transurethral thulium laser prostatectomy was 9.62% (5/52), the short-term incontinence rate was 11.54% (5/52), and the long-term incontinence rate was 9.62% (5/52). The immediate postoperative incontinence rates for semi-separation, pre-separation, and post- separation were 8.33% (1/12), 8.33% (2/24), and 12.5% (2/16), respectively. The short-term incontinence rates for semi-separation, pre-separation, and post-separation were 8.33% (1/12), 8.33% (2/24), and 18.75% (3/16), respectively. The long-term incontinence rates for semi-separation, pre-separation, and post-separation were 8.33% (1/12), 8.33% (2/24), and 12.5% (2/16), respectively. CONCLUSIONS: The incidence of urinary incontinence following transurethral thulium laser prostatectomy was lower with semi-separation and pre-separation compared to post-separation.

Risk factor analysis and nomogram construction in patients with distant metastatic prostate cancer at different PSA levels: a study based on the SEER database.

OBJECTIVE: Prostate cancer (PCa) is the most common malignant tumor in the male genitourinary system. Once PCa has metastasized, it is very difficult to cure. The purpose of this study was to investigate the prognostic risk factor analysis of patients with different prostate-specific antigen (PSA) levels in distant metastatic PCa. At the same time, we construct effective models for predicting the survival rate of prostate cancer patients. PATIENTS AND METHODS: Data on prostate cancer patients with the presence of distant metastases were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. PCa patients with distant metastases were categorized into two groups based on PSA levels, one with PSA <20 ng/mL and the other with PSA ≥20 ng/mL. Univariate and multivariate COX regression analyses were used to identify independent factors affecting the prognosis of the patients. A nomogram was constructed using the independent prognostic factors, and the results were evaluated using calibration curves, timeROC curves, and Kaplan-Meier curves. RESULTS: In the PSA <20 ng/mL group, there were a total of 1,832 patients. COX regression analysis showed that age, marital status, N stage, grade, Gleason score, and medical household income inflation were independent prognostic factors for overall survival (OS) in patients. In addition, we found that age, marital status, N stage, bone metastasis, grade, and Gleason score were independent prognostic factors for cancer-specific survival (CSS) in patients. In the PSA ≥20 ng/mL group, there were a total of 5,314 patients. It was found that age, ethnicity, marital status, bone metastasis, first malignant primary indicator, grade, Gleason score, and medical household income inflation were patients' independent prognostic factors for OS. For CSS, we found that age, ethnicity, marital status, T stage, radiotherapy, bone metastasis, Gleason score, and Median household income inflation were independent prognostic factors. Constructing a nomogram can accurately predict the prognosis of this group of patients. CONCLUSIONS: We found different independent prognostic factors for different PSA levels in patients with distant metastatic PCa. A new nomogram was constructed to predict OS and CSS in patients, which helps in clinical-assisted decision-making.

Outcomes of robot-assisted radical prostatectomy in men after trans-urethral resection of the prostate: a matched-pair analysis.

Prior history of transurethral resection of the prostate (TURP) can complicate Robot-assisted radical prostatectomy (RARP). Very few studies analyse the outcomes of RARP in men with a prior history of TURP. We analysed the oncological and functional outcomes of RARP in post-TURP men from our prospectively maintained database. We included the RARP data from January 2016 to January 2022. Thirty men who had RARP with a prior history of TURP were identified (Group 2). They were matched using R software and propensity score matching to 90 men with no previous TURP (Group-1). The groups were matched for age, body mass index (BMI), Gleason score, stage, PSA and D'Amico risk category in a 1:3 ratio. The two-year oncological and functional outcomes were compared. Overall, the study found no significant difference between the groups in the preoperative parameters, such as BMI, age, Gleason grade, clinical stage, PSA, prostate volume, and D'amico risk grouping. There was no difference in the estimated blood loss. The TURP group had a lower chance of having a nerve spare (p = 0.03). The median console time was longer in the TURP group (140 min (120,180) versus 168 (129,190) p = 0.058). The postoperative complications (Clavien-Dindo 3a 2% versus 6.7%) and hospital stay (median of 2 days), positive surgical margins, continence, and biochemical recurrence rates at 3, 12, and 24 months were not statistically different between the groups. In high-volume centres, the oncological and continence outcomes of RARP post-TURP are not inferior to that of men without prior TURP.

Prediction of false-positive PI-RADS 5 lesions on prostate multiparametric MRI: development and internal validation of a clinical-radiological characteristics based nomogram.

BACKGROUND: To develop a risk model including clinical and radiological characteristics to predict false-positive The Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. METHODS: Data of 612 biopsy-naïve patients who had undergone multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy were collected. Clinical variables and radiological variables on mpMRI were adopted. Lesions were divided into the training and validation cohort randomly. Stepwise multivariate logistic regression analysis with backward elimination was performed to screen out variables with significant difference. A diagnostic nomogram was developed in the training cohort and further validated in the validation cohort. Calibration curve and receiver operating characteristic (ROC) analysis were also performed. RESULTS: 296 PI-RADS 5 lesions in 294 patients were randomly divided into the training and validation cohort (208 : 88). 132 and 56 lesions were confirmed to be clinically significant prostate cancer in the training and validation cohort respectively. The diagnostic nomogram was developed based on prostate specific antigen density, the maximum diameter of lesion, zonality of lesion, apparent diffusion coefficient minimum value and apparent diffusion coefficient minimum value ratio. The C-index of the model was 0.821 in the training cohort and 0.871 in the validation cohort. The calibration curve showed good agreement between the estimation and observation in the two cohorts. When the optimal cutoff values of ROC were 0.288 in the validation cohort, the sensitivity, specificity, PPV, and NPV were 90.6%, 67.9%, 61.7%, and 92.7% in the validation cohort, potentially avoiding 9.7% unnecessary prostate biopsies. CONCLUSIONS: We developed and validated a diagnostic nomogram by including 5 factors. False positive PI-RADS 5 lesions could be distinguished from clinically significant ones, thus avoiding unnecessary prostate biopsy.

Machine learning pipeline to analyze clinical and proteomics data: experiences on a prostate cancer case.

Proteomic-based analysis is used to identify biomarkers in blood samples and tissues. Data produced by devices such as mass spectrometry requires platforms to identify and quantify proteins (or peptides). Clinical information can be related to mass spectrometry data to identify diseases at an early stage. Machine learning techniques can be used to support physicians and biologists in studying and classifying pathologies. We present the application of machine learning techniques to define a pipeline aimed at studying and classifying proteomics data enriched using clinical information. The pipeline allows users to relate established blood biomarkers with clinical parameters and proteomics data. The proposed pipeline entails three main phases: (i) feature selection, (ii) models training, and (iii) models ensembling. We report the experience of applying such a pipeline to prostate-related diseases. Models have been trained on several biological datasets. We report experimental results about two datasets that result from the integration of clinical and mass spectrometry-based data in the contexts of serum and urine analysis. The pipeline receives input data from blood analytes, tissue samples, proteomic analysis, and urine biomarkers. It then trains different models for feature selection, classification and voting. The presented pipeline has been applied on two datasets obtained in a 2 years research project which aimed to extract hidden information from mass spectrometry, serum, and urine samples from hundreds of patients. We report results on analyzing prostate datasets serum with 143 samples, including 79 PCa and 84 BPH patients, and an urine dataset with 121 samples, including 67 PCa and 54 BPH patients. As results pipeline allowed to identify interesting peptides in the two datasets, 6 for the first one and 2 for the second one. The best model for both serum (AUC=0.87, Accuracy=0.83, F1=0.81, Sensitivity=0.84, Specificity=0.81) and urine (AUC=0.88, Accuracy=0.83, F1=0.83, Sensitivity=0.85, Specificity=0.80) datasets showed good predictive performances. We made the pipeline code available on GitHub and we are confident that it will be successfully adopted in similar clinical setups.

Isoform-independent promotion of contractility and proliferation, and suppression of survival by with no lysine/K kinases in prostate stromal cells.

With no lysine/K kinases (WNKs) promote vasocontraction and vascular smooth muscle cell proliferation. In the prostate, smooth muscle contraction and growth may be critical for the development and medical treatment of voiding symptoms in benign prostatic hyperplasia. Here, we examined the effects of isoform-specific WNK silencing and of the WNK inhibitor WNK463 on growth-related functions and contraction in prostate stromal cells, and in human prostate tissues. Impacts of WNK silencing by transfection of cultured stromal cells with isoform-specific siRNAs were qualitatively and quantitatively similar for each WNK isoform. Effects of silencing were largest on cell death (3-5 fold increase in annexin V-positive/7-AAD-positive cells), on proliferation rate, Ki-67 mRNA expression and actin organization (reduced around two-thirds). Contraction in matrix contraction assays and viability were reduced to a lower degree (approximately half), but again to a similar extent for each WNK isoform. Effects of silencing were quantitatively and qualitatively reproduced by 10 µM WNK463, while 1 µM still induced cell death and breakdown in actin organization, without affecting proliferation or viability. Using 500 nM and 10 µM, WNK463 partly inhibited neurogenic and U46619-induced contractions of human prostate tissues (around half), while inhibition of α1-adrenergic contractions (around half) was limited to 10 µM. All four WNK isoforms suppress cell death and promote proliferation in prostate stromal cells. WNK-driven contraction of stromal cells appears possible, even though to a limited extent. Outcomes of isoform-specific WNK silencing can be fully reproduced by WNK463, including inhibition of smooth muscle contraction in human prostate tissues, but require high concentrations.

Long Non-Coding RNA NUTM2A-AS1/miR-376a-3p/PRMT5 Axis Promotes Prostate Cancer Progression.

BACKGROUND: In recent years, significant attention has been directed towards long non-coding RNA NUT family member 2A antisense RNA 1 (NUTM2A-AS1) for its oncogenic role in tumours. This study aimed to investigate the functional and molecular mechanisms underlying NUTM2A-AS1 in prostate cancer (PCa). METHODS: NUTM2A-AS1, miR-376a-3p, and protein arginine methyltransferase 5 (PRMT5) levels were assessed in PCa samples and matched non-cancerous prostate samples. The DU145 cell line was conditioned to undergo transfection with relevant plasmids, and a cell counting kit-8 assay was performed to evaluate cell proliferation. A Transwell assay was conducted to analyse cell migration or invasion. Cell apoptosis was assessed using an annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit and flow cytometry. A tumour sphere formation assay was conducted to assess the ability of PCa cells to form tumour spheres. RESULTS: We found elevated expression of NUTM2A-AS1 and PRMT5 and decreased expression of miR-376a-3p in PCa samples. Inhibition of NUTM2A-AS1 or overexpression of miR-376a-3p led to reduced cell proliferation and diminished cancer stem cell-like traits in vitro. NUTM2A-AS1 regulated miR-376a-3p through competitive absorption, thereby modulating PRMT5. Up-regulation of PRMT5 nullified the therapeutic effects of inhibiting NUTM2A-AS1 or overexpressing miR-376a-3p in DU145 cells. CONCLUSIONS: NUTM2A-AS1 promotes cancer stem cell-like traits in PCa cells by targeting PRMT5 through miR-376a-3p. Therefore, these NUTM2A-AS1-based novel insights into tumour therapy hold promise for patients with PCa.

Dishevelled Segment Polarity Protein 3 (DVL3) Induced by Bacterial LPS Promotes the Proliferation and Migration of Prostate Cancer Cells through the TLR4 Pathway.

BACKGROUND: Chronic inflammation is associated with various malignant tumors. Bacterial lipopolysaccharides (LPSs) play a significant part in the event and development of prostate cancer. Dishevelled segment polarity protein 3 (DVL3) is a shared component of the Wnt/ß-catenin and Notch signaling pathways, which are involved in tumor progression, chemoresistance, and maintenance of stem cell-like properties. According to reports, prostatic cancer cell invasion and proliferation are mediated by toll-like receptor 4 (TLR4). However, the role and regulation of DVL3 in prostate cancer and its relationship with TLR4 remain unclear. METHODS: Survival curves were plotted to evaluate the relationship between DVL3 expression and prognosis in patients with prostate cancer. DVL3 was silenced in PC3 and DU145 cells using small interfering RNAs (siRNAs). Subsequently, cell counting kit-8 (CCK-8) assay, colony formation assay, transwell migration assay, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) were performed to investigate the role of DVL3 in cell proliferation and migration in vitro. The protein markers of potential pathways were analyzed via western blotting. RESULTS: DVL3 expression was linked to prognosis in patients with prostate cancer; In particular, patients with high DVL3 expression had a poor prognosis. LPS stimulation increased (p < 0.01) the expression of DVL3 in PC3 cells. DVL3 regulated tumor cell proliferation and migration by mediating the increase (p < 0.01) in TLR4 expression. Knockout of TLR4 validated that TLR4 played a crucial role in LPS-induced DVL3 expression. Silencing of DVL3 decreased (p < 0.01) the LPS-induced proliferation and migration of PC3 cells. CONCLUSIONS: Bacterial LPS-induced DVL3 promoted the multiplication and migration of prostate cancer cells through the TLR4 pathway. This study offers a valuable reference for the development and clinical application of targeted drugs for prostate cancer.

Giant Midline Prostatic Cyst: An Unusual Cause of Acute Urinary Retention.

Midline prostatic cysts are infrequent and mostly asymptomatic. We presented a striking case of a giant midline cyst and detailed its diagnosis, evolution, and treatment. From this case, we offered a comparison of congenital intraprostatic midline cysts, namely, Müller's cysts and utricle cysts. A 40-year-old male experienced recurrent urinary retention. A 10 × 11 mm2 cyst in the mid-prostatic region was diagnosed through transrectal ultrasound, leading to a transperineal puncture as a minimally invasive intervention. Seven years later, the cyst recurred, manifesting obstructive symptoms such as a weak urinary stream, frequent urination, and residual urine sensation. Laparoscopic surgery was then performed for the confirmed 98 × 13 mm2 cystic recurrence. The postoperative course was favourable with no complications. Symptoms were completely resolved, which was maintained over a three-year follow-up period. The therapeutic approach to midline cysts targets symptomatic cases or infertility, ranging from cyst puncture to transurethral endoscopic treatment. Recurrence after minimally invasive interventions is a challenge, with laparoscopic surgery as an alternative post-failed conservative approach. Although total cyst removal risks adjacent structure damage, marsupialisation improves the clinical outcomes. In summary, symptomatic midline prostatic cysts present challenges owing to recurrences after minimally invasive approaches. Enhanced laparoscopic techniques offer a solution, particularly in highly symptomatic cases requiring definitive treatment, as illustrated by this outstanding case report.

Assessment of the accuracy of biparametric MRI/TRUS fusion-guided biopsy for index tumor evaluation using postoperative pathology specimens.

BACKGROUND: Multiparametric MRI (mpMRI) is widely used for the diagnosis, surveillance, and staging of prostate cancer. However, it has several limitations, including higher costs, longer examination times, and the use of gadolinium-based contrast agents. This study aimed to investigate the accuracy of preoperatively assessed index tumors (ITs) using biparametric MRI (bpMRI)/transrectal ultrasound (TRUS) fusion biopsy compared with radical prostatectomy (RP) specimens. METHODS: We included 113 patients diagnosed with prostate cancer through bpMRI/TRUS fusion-guided biopsies of lesions with a Prostate Imaging Reporting and Data System (PI-RADS) category ≥ 3. These patients underwent robot-assisted laparoscopic radical prostatectomy (RARP) at our institution between July 2017 and March 2023. We examined the localization of preoperative and postoperative ITs, the highest Gleason score (GS), and tumor diameter in these patients. RESULTS: The preoperative cT stage matched the postoperative pT stage in 53 cases (47%), while 31 cases (27%) were upstaged, and 29 cases (26%) were downstaged (Weighted Kappa = 0.21). The preoperative and postoperative IT localizations were consistent in 97 cases (86%). The concordance rate between Gleason groups in targeted biopsies and RP specimens was 51%, with an upgrade in 25 cases (23%) and a downgrade in 27 cases (25%) (Weighted Kappa = 0.42). The maximum diameter of the IT and the maximum cancer core length on biopsy were correlated with the RP tumor's maximum diameter (p < 0.001 for both). CONCLUSION: The diagnostic accuracy of bpMRI/TRUS fusion biopsy is comparable to mpMRI, suggesting that it can be a cost-effective and time-saving alternative.

Identification of ferroptosis related genes and pathways in prostate cancer cells under erastin exposure.

BACKGROUND: Few studies are focusing on the mechanism of erastin acts on prostate cancer (PCa) cells, and essential ferroptosis-related genes (FRGs) that can be PCa therapeutic targets are rarely known. METHODS: In this study, in vitro assays were performed and RNA-sequencing was used to measure the expression of differentially expressed genes (DEGs) in erastin-induced PCa cells. A series of bioinformatic analyses were applied to analyze the pathways and DEGs. RESULTS: Erastin inhibited the expression of SLC7A11 and cell survivability in LNCaP and PC3 cells. After treatment with erastin, the concentrations of malondialdehyde (MDA) and Fe2+ significantly increased, whereas the glutathione (GSH) and the oxidized glutathione (GSSG) significantly decreased in both cells. A total of 295 overlapping DEGs were identified under erastin exposure and significantly enriched in several pathways, including DNA replication and cell cycle. The percentage of LNCaP and PC3 cells in G1 phase was markedly increased in response to erastin treatment. For four hub FRGs, TMEFF2 was higher in PCa tissue and the expression levels of NRXN3, CLU, and UNC5B were lower in PCa tissue. The expression levels of SLC7A11 and cell survivability were inhibited after the knockdown of TMEFF2 in androgen-dependent cell lines (LNCaP and VCaP) but not in androgen-independent cell lines (PC3 and C4-2). The concentration of Fe2+ only significantly increased in TMEFF2 downregulated LNCaP and VCaP cells. CONCLUSION: TMEFF2 might be likely to develop into a potential ferroptosis target in PCa and this study extends our understanding of the molecular mechanism involved in erastin-affected PCa cells.