Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype ...Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype or develop resistance to therapeutic interventions,leading to tumor metastasis and a poorer prognosis.When PC metastasizes to distant sites,the bone remains the predominant location,and brain metastases are regarded as exceedingly rare.Case Description:The current study focused on a rare clinical PC case that presented multiple brain metastases after prostate surgery.The patient was initially diagnosed with PC through prostate biopsy and subsequently underwent prostate debulking surgery while continuing androgen deprivation therapy,which maintained low prostatespecific antigen(PSA)levels for 4 years.However,a sudden PSA surge to 7.858 ng/mL led to the emergence of two brain metastatic tumors,which were confirmed to have originated from the prostate.Conclusions:Patients with advanced PC require comprehensive evaluations to detect rare metastatic sites,such as the brain,to avoid missed diagnoses.For patients with brain metastases,a multimodal approach combining surgical resection,postoperative radiotherapy,and endocrine therapy can effectively alleviate symptoms and enhance survival.展开更多
Background Neuroendocrine prostate cancer(NEPC)is an aggressive subtype of castration-resistant prostate cancer(CRPC)that is typically resistant to nearly all current therapies.Methods In this study,single-cell RNA se...Background Neuroendocrine prostate cancer(NEPC)is an aggressive subtype of castration-resistant prostate cancer(CRPC)that is typically resistant to nearly all current therapies.Methods In this study,single-cell RNA sequencing(scRNA-seq)and bioinformatic analysis identified centrosomal protein 55(CEP55)as a critical factor in the transformation from hormone-sensitive prostate cancer(HSPC)to CRPC and,ultimately to,NEPC.Results Subsequent bioinformatics analyses and clinical sample validation showed that CEP55 is significantly upregulated in NEPC tissues relative to HSPC and CRPC.Furthermore,while CEP55 show no significant association with the immune microenvironment or cancer-associated fibroblasts(CAFs),our findings indicated that it directly mediates the plasticity of prostate cancer cells,thereby driving NEPC progression.Specifically,in vivo and in vitro experiments confirmed that CEP55 enhances cell proliferation,migration,invasion and the expression of NEPC biomarkers in prostate cancer.Importantly,although cisplatin is the primary treatment for NEPC clinically,CEP55 has been shown to regulate cisplatin resistance through the phosphorylation of cyclin-dependent kinase 1(CDK1)at the tyrosine 15(Tyr15)site.Conclusions In summary,our study identifies a key gene that influences the neuroendocrine differentiation process in prostate cancer,suggesting its potential as an important therapeutic target.展开更多
Background:The Da Vinci Single-Port Robotic System(Da Vinci-SP),introduced by Intuitive(CA,USA)in 2018 in the USA and in 2024 in Europe,integrates advanced features like a flexible camera and articulating instruments....Background:The Da Vinci Single-Port Robotic System(Da Vinci-SP),introduced by Intuitive(CA,USA)in 2018 in the USA and in 2024 in Europe,integrates advanced features like a flexible camera and articulating instruments.It has garnered significant interest in urology.Our report presents the first described European series of Radical Prostatectomies using the Da Vinci SP at the leading Italian center,Istituto Nazionale Tumori di Napoli,IRCCS“G.Pascale”Foundation,detailing the technical differences and challenges faced by experienced multiport robotic surgeons.Methods:Sixteen patients have been enrolled and underwent Single-Port(SP)Robot-Assisted Radical Prostatectomy(SP-RARP).Baseline characteristics of the patients were collected.We provided a step-by-step description of the surgical technique.Oncological outcomes have been evaluated and compared with magnetic resonance imaging(MRI)and biopsy results.Intraoperative,perioperative,and postoperative complications,surgical outcomes,functional outcomes,and technical issues of the new system were also documented.Results:All surgeries were successfully performed without the need for conversion.An extraperitoneal approach was used for all patients.Median Console time was 110 min.No complications were reported.The estimated median blood loss was 175 cc.Discharge from the hospital was on the first post-operative day for all patients.Bladder catheter removal was on day 7 without the need for cystography.Conclusions:We presented the first European case series of SP-RARP,reporting our experience and confirming the procedure’s feasibility for a highly experienced robotic surgeon.Experience with an extraperitoneal approach using the multiport(MP)platform,combined with well-conducted training for the SP system,may facilitate the transition to SP surgery.Further procedures and studies are needed to evaluate the oncological and functional outcomes.展开更多
Background:Low-dose rate(LDR)prostate brachytherapy is a recommended treatment of localized prostate cancer in current guidelines.The study aimed to determine biochemical relapse-free survival(BRFS)in patients treated...Background:Low-dose rate(LDR)prostate brachytherapy is a recommended treatment of localized prostate cancer in current guidelines.The study aimed to determine biochemical relapse-free survival(BRFS)in patients treated with dynamic real-time low-dose rate(LDR)brachytherapy using Iodine 125(I^(125)).Methods:We retrospectively reviewed 499 patients with localized prostate cancer treated with I^(125) LDR realtime brachytherapy between 2003 and 2021.The mean patient age was 65 years(range:45–84 years).Based on the National Comprehensive Cancer Network(NCCN)risk classification,230 patients(46.1%)were categorized as low risk,235(47.1%)as intermediate risk,and 34(6.8%)as high risk.Gleason scores were distributed as follows:3+3 in 283 cases(56.7%),3+4 in 157 cases(31.5%),4+3 in 46 cases(9.2%),and 4+4 in 13 cases(2.6%).The mean follow-up was 70.5 months.Results:Tumor relapse was observed in 47 patients(9.4%)over a mean follow-up period of 6.26 years(SD 4.16).Local recurrence within the prostate occurred in 20 cases(4%).Patients with nadir PSA<0.2 ng/mL at 5 years of follow-up had a significantly lower incidence of tumor recurrence(3%)compared to those with a nadir PSA>0.2 ng/mL(21.9%)(p=0.0001).Biochemical relapse-free(BRFS)rates at 5,10 and 15 years were 96%,91.5% and 88.9%,respectively.When stratified by NCCCN risk groups,5-year BRFS was 96% in low risk,98% in intermediate risk and 85% in high risk patients(p=0.003).Inmultivariate analysis,only age at the time of brachytherapy(p=0.009),initial PSA(p=0.007)and Gleason grade(p=0.007)were significantly associated with tumor recurrence.Cancer-specific survival and overall survival were 99.8% and 98.0%,respectively.Conclusions:LDR with I^(125) has excellent longterm oncological outcomes for patients with low and intermediate-risk prostate cancer,in particular,patients achieving a nadir PSA<0.2 ng/mL at 5 years post-treatment.展开更多
Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated signi...Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.展开更多
Objectives:PSMA PET/CT(Prostate-Specific MembraneAntigen Positron Emission Tomography/Computed Tomography)offers improved accuracy in detecting lymph node invasion(LNI)in prostate cancer(PC)patients,potentially reduci...Objectives:PSMA PET/CT(Prostate-Specific MembraneAntigen Positron Emission Tomography/Computed Tomography)offers improved accuracy in detecting lymph node invasion(LNI)in prostate cancer(PC)patients,potentially reducing the need for extended pelvic lymph node dissection(ePLND).This study aims to evaluate a patient-tailored care pathway in which ePLND is performed only in patients with unfavorable intermediate-or high-risk PC who are deemed at risk for LNI based on PSMA PET/CT findings.Methods:In this interventional cohort study,81 patients were managed according to the new care pathway.ePLND was omitted in cases of negative PSMA PET/CT findings(N0M0),while those with positive PSMA PET/CT findings(N1M0)underwent ePLND.A comparator group of 81 patients was selected from a prospectively generated database for comparison.Results:The intervention group experienced a 75% reduction in the number of ePLNDs performed compared to the comparator group(p<0.001).ePLND-related complications were significantly lower in the intervention group(p=0.008).No significant difference was observed in 3-year biochemical-recurrence free survival(BRFS)between the two groups(p=0.958).Conclusion:Omitting ePLND in patients with negative PSMA PET/CT findings(N0M0)leads to a substantial reduction in the number of ePLNDs performed,resulting in a decrease in morbidity,without compromising early oncological outcomes.展开更多
Overview:Surgical management of benign prostatic hyperplasia(BPH)has evolved significantly,incorporating various minimally invasive procedures aimed at reducing morbidity and optimizing patient outcomes.Despite advanc...Overview:Surgical management of benign prostatic hyperplasia(BPH)has evolved significantly,incorporating various minimally invasive procedures aimed at reducing morbidity and optimizing patient outcomes.Despite advancements,transurethral approaches continue to pose risks such as urethral strictures and urinary incontinence due to mechanical and thermal stress.To address these limitations,the Suprapubic Transvesical Adenoma Resection of the Prostate(STARP)was developed,offering a direct suprapubic route that bypasses the urethra entirely.Recent studies have validated STAR-P as both feasible and safe,emphasizing advantages such as enhanced visualization of the urinary sphincter,minimized urethral trauma,effective hemostasis,and reduced operative stress.The procedure utilizes specially designed instrumentation,including a large-caliber bipolar resectoscope(42 Fr),allowing the efficient removal of substantial adenoma tissue in fewer resection passes compared to traditional methods.Objectives:This article provides a comprehensive,step-by-step description of the STAR-P technique.The primary objective is to detail patient selection criteria,preoperative assessments,procedural steps including mini-open suprapubic access,specialized instrumentation usage,resection techniques,and postoperative management protocols.Highlighting technical considerations and procedural innovations aims to inform urologists about the potential benefits of STAR-P,particularly in patients at higher risk for urethral complications or those with large prostate volumes.By documenting the procedural intricacies and outcomes clearly and thoroughly,we seek to encourage informed adoption of STAR-P as an alternative,effective surgical approach for managing benign prostatic hyperplasia,thus contributing to the evolving landscape ofminimally invasive urological surgery.展开更多
Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(P...Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.展开更多
Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim ...Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.展开更多
Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly can...Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly cancer-associated fibroblasts(CAFs),as a critical determinant of disease behavior.CAFs constitute a heterogeneous population originating from fibroblasts,mesenchymal stem cells,endothelial cells,epithelial cells undergoing epithelial-mesenchymal transition(EMT),and adipose tissue.Through dynamic crosstalk with tumor,immune,endothelial,and adipocyte compartments,CAFs orchestrate oncogenic processes including tumor proliferation,invasion,immune evasion,extracellular matrix remodeling,angiogenesis,and metabolic reprogramming.This review comprehensively summarizes the cellular origins,phenotypic and functional heterogeneity,and spatial distribution of CAFs within the prostate TME.We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance,and critically evaluate emerging strategies to therapeutically target CAFmediated signaling,metabolic,and immune pathways.By integrating recent advances from single-cell and spatial transcriptomics(ST),our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.展开更多
Objective:To identify chromatin regulators(CRs)-based molecular subtypes and risk scores for accurately predicting biochemical recurrence(BCR)after radical prostatectomy(RAP)in prostate cancer(PCa)patients.Methods:Dif...Objective:To identify chromatin regulators(CRs)-based molecular subtypes and risk scores for accurately predicting biochemical recurrence(BCR)after radical prostatectomy(RAP)in prostate cancer(PCa)patients.Methods:Differentially expressed genes(DEGs)between tumor and normal samples from The Cancer Genome Atlas(TCGA)and gene expression omnibus(GEO)databases were intersected with CR-related and prognostic genes.Consensus clustering,risk score analysis,functional analysis,immune microenvironment,m6A,and heterogeneity assessments were performed using R software.In vitro validation used DU145 and C42B PCa cell lines.Topoisomerase II alpha(TOP2A)was knocked down via si RNA.Assays included CCK-8 proliferation,colony formation,transwell migration/invasion,wound healing,and western blotting(WB)for pathway validation.Results:TOP2A and peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PPARGC1A)defined molecular subtypes and a risk score in TCGA,validated in a GEO dataset.Cluster 2 exhibited significantly shorter BCR-free survival vs.cluster 1 in TCGA[hazard ratio(HR):2.21;95%confidence interval(95%CI):1.32-3.73;P=0.003],GEO(HR:2.05;95%CI:1.05-4.02;P=0.010),and MSKCC2010(HR:5.93;95%CI:1.96-17.87;P<0.001).Similar survival differences were observed between high-and low-risk groups(defined by the median risk score).Cluster 2 showed greater tumor heterogeneity and higher m6A gene expression.Gene set variation analysis(GSVA)revealed downregulated cell-cycle pathways in cluster 2,alongside suppressed tumor-infiltrating immune cells.TOP2A knockdown significantly impaired PCa cell proliferation,colony formation,migration,and invasion.Mechanistically,it suppressed phosphoinositide 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)pathway activation,reducing phosphorylated PI3K and AKT levels without altering total protein.Conclusions:TOP2A and PPARGC1A effectively stratify PCa subtypes for RAP patients.TOP2A drives malignant progression via the PI3K/AKT pathway.展开更多
Objectives:Prostate cancer(PCa)is a highly prevalent male malignancy with limited efficacy in advanced stages.Dysregulated modulation of necroptosis was reported to be tightly correlated with PCa initiation and progre...Objectives:Prostate cancer(PCa)is a highly prevalent male malignancy with limited efficacy in advanced stages.Dysregulated modulation of necroptosis was reported to be tightly correlated with PCa initiation and progression.Herein,we aimed to identify necroptosis-associated long non-coding RNAs(lncRNAs)and delineate their functional roles in PCa through an integrated approach combining bioinformatic analyses and in vitro experimental validation.Methods:RNA sequencing data and corresponding clinical information of PCa were downloaded from The Cancer Genome Atlas(TCGA).Differentially expressed necroptosis-related genes(NRGs)and lncRNAs were screened,and necroptosis activity was assessed by single-sample gene set enrichment analysis(ssGSEA).Weighted Gene Co-expression Network Analysis(WGCNA)identified necroptosis-related lncRNA modules,with key lncRNAs prioritized via Cox regression.Clinical correlation analyses and in vitro experiments validated the function of the key lncRNA LINC00595.Results:A total of 50 differentially expressed NRGs were identified,among which pro-necroptotic genes exhibited pronounced downregulation,while anti-necroptotic genes were significantly upregulated.Consistently,ssGSEA confirmed reduced necroptosis activity in PCa.WGCNA further identified 13 core necroptosis-related lncRNAs(NRlncRNAs),with Cox regression analysis pinpointing LINC00595 and LINC00908 as the top prognostic candidates.Both lncRNAs were downregulated in PCa,with low expression correlating with advanced T stage,lymph node metastasis,and poor prognosis.Functional experiments demonstrated that LINC00595 overexpression inhibited PCa cell proliferation,migration,and invasion,and enhanced necroptosis.Conclusions:Collectively,our findings identified LINC00595 and LINC00908 as novel regulators of necroptosis in PCa.Specifically,LINC00595 exerted tumor-suppressive effects by enhancing necroptosis,holding potential as prognostic biomarkers and therapeutic targets.展开更多
Objective:Androgen receptor(AR)signaling is a central driver of prostate cancer progression,yet the metabolic and transcriptional mechanisms regulating AR expression remain incompletely characterized.This study invest...Objective:Androgen receptor(AR)signaling is a central driver of prostate cancer progression,yet the metabolic and transcriptional mechanisms regulating AR expression remain incompletely characterized.This study investigated whether the immunoproteasome inhibitor ONX-0914 suppresses hormone-sensitive prostate cancer(HSPC)through metabolic modulation of AR and aimed to identify the transcriptional mediator involved.Methods:HSPC and castration-resistant prostate cancer models were used to evaluate the effects of ONX-0914 on cell proliferation,invasion,migration,and epithelial-mesenchymal transition.Xenograft assays,bioinformatic screening,and analyses of O-GlcNAcylation and protein stability were performed,together with quantitative polymerase chain reaction(qPCR)and Western blotting.Results:ONX-0914 markedly suppressed hormone-sensitive prostate cancer(HSPC)progression through both LMP7-dependent and LMP7-independent mechanisms.Mechanistically,ONX-0914 activated the hexosamine biosynthetic pathway and enhanced global O-GlcNAcylation,leading to stabilization of the transcriptional repressor Transcription factor 7-like 1(TCF7L1)and consequent suppression of androgen receptor(AR)expression.Functionally,activation of the O-GlcNAcylation-TCF7L1 axis inhibited cell proliferation,invasion,migration,and epithelial-mesenchymal transition in vitro.In vivo,TCF7L1 overexpression,particularly under conditions of enhanced O-GlcNAcylation,significantly suppressed tumor growth and AR expression.Conclusion:This study identifies a novel ONX-0914/HBP/TCF7L1 O-GlcNAcylation axis that metabolically stabilizes TCF7L1,leading to repression of AR signaling and inhibition of HSPC progression.These findings reveal a previously unrecognized metabolic-transcriptional regulatory mechanism and highlight TCF7L1 O-GlcNAcylation as a potential therapeutic target in AR-dependent prostate cancer.展开更多
Objective:Prostate cancer is the second most common fatal cancer in men.Identifying new biological therapeutic targets is crucial to effectively improve the prognosis of prostate cancer patients.Ovarian tumor family d...Objective:Prostate cancer is the second most common fatal cancer in men.Identifying new biological therapeutic targets is crucial to effectively improve the prognosis of prostate cancer patients.Ovarian tumor family deubiquitinase 4(OTUD4)is a member of the ovarian tumor-associated protease domain(OTUDs)family.Although previous studies have shown that the expression and function of OTUD4 vary across different tumors,its role in prostate cancer remains unknown.The aim of this study is to explore new therapeutic targets and diagnostic markers for prostate cancer and investigate their mechanisms of action.Methods:Cell culture,Cell Counting Kit-8(CCK-8)assay,colony formation assay,Transwell assay,5-Ethynyl-2′-deoxyuridine(EdU)assay,immunofluorescence,Western blot,Quantitative real-time PCR(qRT-PCR),protein mass spectrometry,nude mouse xenograft models,immunohistochemistry(IHC),and hematoxylin and eosin(H&E)staining were utilized.Results:We found that OTUD4 expression was reduced in prostate cancer and negatively correlated with poor prognosis in both in vivo and in vitro experiments.Subsequent mechanistic studies revealed that OTUD4 directly inhibits the degradation of myosin-9(MYH9)protein via deubiquitination.Although MYH9 has been previously reported to act as a tumor suppressor in prostate cancer,no experimental evidence had demonstrated that MYH9 inhibits prostate cancer growth.Our results indicate that MYH9 overexpression effectively suppresses prostate cancer through interactions with cell adhesion molecules.Conclusion:Collectively,these results suggest that OTUD4 functions as a tumor suppressor in prostate cancer.Specifically,OTUD4 inhibits MYH9 degradation via deubiquitination,thereby enabling MYH9-mediated suppression of prostate cancer.展开更多
Radical prostatectomy is a commonly used surgical method in cases of localized prostate cancer.In recent years,with the advent of new medical technologies and surgical techniques,the evolution of radical prostatectomy...Radical prostatectomy is a commonly used surgical method in cases of localized prostate cancer.In recent years,with the advent of new medical technologies and surgical techniques,the evolution of radical prostatectomy has revolutionized,especially in robot-assisted radical prostatectomy(RARP).The evolution of surgical approaches for radical prostatectomy has occurred in three stages:open surgery,laparoscopic intervention,and robot-assisted surgery.Regarding the functional recovery of patients who underwent laparoscopic radical prostatectomy or RARP,with the improvement of disease conditions,oncological prognosis of patients was not compromised.Particularly,RARP boasts distinguished novel techniques and approaches for maintaining urinary continence and sexual function in the short-and long-term.In addition,studies in the last two decades have shown its correlation with decreasing postoperative morbidity.In this paper,the available literatures related to the surgical approaches ranging from open surgery to RARP were reviewed,the superiority of any novel procedure was analyzed,and the advantages and disadvantages among the three modalities were compared,hoping to provide guidance to urologists when considering surgical approaches in the treatment of localized prostate cancer.展开更多
In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen （PSA） testin...In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen （PSA） testing remains very low compared with Western countries, and the benefits of population-based screening remain unclear. This review describes the current status of population screening and diagnosis for prostate cancer in Japan and discusses the efficacy of population screening for the Asian population. Since the 1990s, screening systems have been administered by each municipal government in Japan, and decreases in the prostate cancer mortality rate are expected in some regions where the exposure rate to PSA screening has increased markedly. A population-based screening cohort revealed that the proportion of metastatic disease in cancer detected by screening gradually decreased according to the increased exposure rate, and a decreasing trend in the proportion of cancer with high serum PSA levels after population screening was started. The prognosis of the prostate cancer detected by population screening was demonstrated to be more favorable than those diagnosed outside of the population screening. Recent results in screening cohorts demonstrated the efficacy of PSA. These recent evidences regarding population-based screening in Japan may contribute to establishing the optimal prostate cancer screeninK system in Asian individuals.展开更多
Objective:To explore clinicopathological predictors of adverse pathological changes(APCs)(upgrading,upstaging,and positive surgical margin[PSM])after robot-assisted radical prostatectomy(RARP)in clinical tumor stage 2...Objective:To explore clinicopathological predictors of adverse pathological changes(APCs)(upgrading,upstaging,and positive surgical margin[PSM])after robot-assisted radical prostatectomy(RARP)in clinical tumor stage 2c(cT2c)prostate cancer(PCa)patients.Methods:From January 2018 to December 2022,cT2cN0M0 PCa patients who underwent prostate biopsies and subsequent RARP at the Peking University First Hospital with an interval between biopsy and RARP of ≤90 days were included.Univariable and stepwise multivariable logistic regression analyses were performed to identify independent risk factors associated with APCs.Nomograms were constructed based on these predictive models.The performance of the nomograms was evaluated by receiver operating characteristic curves,decision curve analyses,and calibration plots.Results:A total of 423 eligible cT2cN0M0 PCa patients were included.The rates of upgrading,upstaging,and PSM in our cohortwere 33%,51%,and 35%,respectively.The stepwise multivariate logistic analysis suggested that PSA density and the percentage of positive cores in systematic biopsy were significantly associated with the occurrence of APCs.The score of the Prostate Imaging Reporting and Data System,PSA density,and the International Society of Urological Pathology grade group(IGG)of needle-biopsy specimens(or clinical IGG[cIGG])were significantly associated with upgrading.The PSA density,percentage of positive cores in systematic biopsy,and largest tumor percentage in all cores of each patient(LTP)were significantly associated with upstaging.The PSA density and LTP were significantly associatedwith the PSM.Based on these results,four nomogramswere developed.Receiver operating characteristic curves,decision curve analyses,and calibration plots implied that the nomograms exhibited excellent accuracy.Conclusion:The predictive models we developed could help to identify high-risk PCa early,and optimize clinical decisions of cT2cN0M0 PCa patients.展开更多
Background:Prostate cancer is a common malignancy,with many men on active surveillance for localized,low-risk disease also experiencing lower urinary tract symptoms(LUTS)from benign prostatic hyperplasia(BPH).Water Va...Background:Prostate cancer is a common malignancy,with many men on active surveillance for localized,low-risk disease also experiencing lower urinary tract symptoms(LUTS)from benign prostatic hyperplasia(BPH).Water Vapor Thermal Therapy(WVTT)is a minimally invasive BPH treatment,but its safety and efficacy in this setting are unclear.Case Description:We report three men with localized PCa on active surveillance who underwent WVTT for LUTS.Conclusions:WVTT appears safe and potentially effective in treating LUTS,especially in those with lower-risk disease and smaller prostate volumes.Further research is needed to confirm safety,efficacy,and optimal patient selection.展开更多
基金supported by the National Natural Science Foundation[Grant Number:82102788]Anhui Province Key Project for Clinical Medical Research Translation and Advancement[202204295107020031,202204295107020007]Anhui Provincial University Excellent Scientific Research and Innovation Team Project[2022AH010071].
文摘Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype or develop resistance to therapeutic interventions,leading to tumor metastasis and a poorer prognosis.When PC metastasizes to distant sites,the bone remains the predominant location,and brain metastases are regarded as exceedingly rare.Case Description:The current study focused on a rare clinical PC case that presented multiple brain metastases after prostate surgery.The patient was initially diagnosed with PC through prostate biopsy and subsequently underwent prostate debulking surgery while continuing androgen deprivation therapy,which maintained low prostatespecific antigen(PSA)levels for 4 years.However,a sudden PSA surge to 7.858 ng/mL led to the emergence of two brain metastatic tumors,which were confirmed to have originated from the prostate.Conclusions:Patients with advanced PC require comprehensive evaluations to detect rare metastatic sites,such as the brain,to avoid missed diagnoses.For patients with brain metastases,a multimodal approach combining surgical resection,postoperative radiotherapy,and endocrine therapy can effectively alleviate symptoms and enhance survival.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(Nos:2024A1515012687)the National Natural Science Foundation of China(No.82303052).
文摘Background Neuroendocrine prostate cancer(NEPC)is an aggressive subtype of castration-resistant prostate cancer(CRPC)that is typically resistant to nearly all current therapies.Methods In this study,single-cell RNA sequencing(scRNA-seq)and bioinformatic analysis identified centrosomal protein 55(CEP55)as a critical factor in the transformation from hormone-sensitive prostate cancer(HSPC)to CRPC and,ultimately to,NEPC.Results Subsequent bioinformatics analyses and clinical sample validation showed that CEP55 is significantly upregulated in NEPC tissues relative to HSPC and CRPC.Furthermore,while CEP55 show no significant association with the immune microenvironment or cancer-associated fibroblasts(CAFs),our findings indicated that it directly mediates the plasticity of prostate cancer cells,thereby driving NEPC progression.Specifically,in vivo and in vitro experiments confirmed that CEP55 enhances cell proliferation,migration,invasion and the expression of NEPC biomarkers in prostate cancer.Importantly,although cisplatin is the primary treatment for NEPC clinically,CEP55 has been shown to regulate cisplatin resistance through the phosphorylation of cyclin-dependent kinase 1(CDK1)at the tyrosine 15(Tyr15)site.Conclusions In summary,our study identifies a key gene that influences the neuroendocrine differentiation process in prostate cancer,suggesting its potential as an important therapeutic target.
文摘Background:The Da Vinci Single-Port Robotic System(Da Vinci-SP),introduced by Intuitive(CA,USA)in 2018 in the USA and in 2024 in Europe,integrates advanced features like a flexible camera and articulating instruments.It has garnered significant interest in urology.Our report presents the first described European series of Radical Prostatectomies using the Da Vinci SP at the leading Italian center,Istituto Nazionale Tumori di Napoli,IRCCS“G.Pascale”Foundation,detailing the technical differences and challenges faced by experienced multiport robotic surgeons.Methods:Sixteen patients have been enrolled and underwent Single-Port(SP)Robot-Assisted Radical Prostatectomy(SP-RARP).Baseline characteristics of the patients were collected.We provided a step-by-step description of the surgical technique.Oncological outcomes have been evaluated and compared with magnetic resonance imaging(MRI)and biopsy results.Intraoperative,perioperative,and postoperative complications,surgical outcomes,functional outcomes,and technical issues of the new system were also documented.Results:All surgeries were successfully performed without the need for conversion.An extraperitoneal approach was used for all patients.Median Console time was 110 min.No complications were reported.The estimated median blood loss was 175 cc.Discharge from the hospital was on the first post-operative day for all patients.Bladder catheter removal was on day 7 without the need for cystography.Conclusions:We presented the first European case series of SP-RARP,reporting our experience and confirming the procedure’s feasibility for a highly experienced robotic surgeon.Experience with an extraperitoneal approach using the multiport(MP)platform,combined with well-conducted training for the SP system,may facilitate the transition to SP surgery.Further procedures and studies are needed to evaluate the oncological and functional outcomes.
文摘Background:Low-dose rate(LDR)prostate brachytherapy is a recommended treatment of localized prostate cancer in current guidelines.The study aimed to determine biochemical relapse-free survival(BRFS)in patients treated with dynamic real-time low-dose rate(LDR)brachytherapy using Iodine 125(I^(125)).Methods:We retrospectively reviewed 499 patients with localized prostate cancer treated with I^(125) LDR realtime brachytherapy between 2003 and 2021.The mean patient age was 65 years(range:45–84 years).Based on the National Comprehensive Cancer Network(NCCN)risk classification,230 patients(46.1%)were categorized as low risk,235(47.1%)as intermediate risk,and 34(6.8%)as high risk.Gleason scores were distributed as follows:3+3 in 283 cases(56.7%),3+4 in 157 cases(31.5%),4+3 in 46 cases(9.2%),and 4+4 in 13 cases(2.6%).The mean follow-up was 70.5 months.Results:Tumor relapse was observed in 47 patients(9.4%)over a mean follow-up period of 6.26 years(SD 4.16).Local recurrence within the prostate occurred in 20 cases(4%).Patients with nadir PSA<0.2 ng/mL at 5 years of follow-up had a significantly lower incidence of tumor recurrence(3%)compared to those with a nadir PSA>0.2 ng/mL(21.9%)(p=0.0001).Biochemical relapse-free(BRFS)rates at 5,10 and 15 years were 96%,91.5% and 88.9%,respectively.When stratified by NCCCN risk groups,5-year BRFS was 96% in low risk,98% in intermediate risk and 85% in high risk patients(p=0.003).Inmultivariate analysis,only age at the time of brachytherapy(p=0.009),initial PSA(p=0.007)and Gleason grade(p=0.007)were significantly associated with tumor recurrence.Cancer-specific survival and overall survival were 99.8% and 98.0%,respectively.Conclusions:LDR with I^(125) has excellent longterm oncological outcomes for patients with low and intermediate-risk prostate cancer,in particular,patients achieving a nadir PSA<0.2 ng/mL at 5 years post-treatment.
文摘Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.
基金supported by a grant from Kom op tegen Kanker(Stand Up to Cancer,Belgium).
文摘Objectives:PSMA PET/CT(Prostate-Specific MembraneAntigen Positron Emission Tomography/Computed Tomography)offers improved accuracy in detecting lymph node invasion(LNI)in prostate cancer(PC)patients,potentially reducing the need for extended pelvic lymph node dissection(ePLND).This study aims to evaluate a patient-tailored care pathway in which ePLND is performed only in patients with unfavorable intermediate-or high-risk PC who are deemed at risk for LNI based on PSMA PET/CT findings.Methods:In this interventional cohort study,81 patients were managed according to the new care pathway.ePLND was omitted in cases of negative PSMA PET/CT findings(N0M0),while those with positive PSMA PET/CT findings(N1M0)underwent ePLND.A comparator group of 81 patients was selected from a prospectively generated database for comparison.Results:The intervention group experienced a 75% reduction in the number of ePLNDs performed compared to the comparator group(p<0.001).ePLND-related complications were significantly lower in the intervention group(p=0.008).No significant difference was observed in 3-year biochemical-recurrence free survival(BRFS)between the two groups(p=0.958).Conclusion:Omitting ePLND in patients with negative PSMA PET/CT findings(N0M0)leads to a substantial reduction in the number of ePLNDs performed,resulting in a decrease in morbidity,without compromising early oncological outcomes.
文摘Overview:Surgical management of benign prostatic hyperplasia(BPH)has evolved significantly,incorporating various minimally invasive procedures aimed at reducing morbidity and optimizing patient outcomes.Despite advancements,transurethral approaches continue to pose risks such as urethral strictures and urinary incontinence due to mechanical and thermal stress.To address these limitations,the Suprapubic Transvesical Adenoma Resection of the Prostate(STARP)was developed,offering a direct suprapubic route that bypasses the urethra entirely.Recent studies have validated STAR-P as both feasible and safe,emphasizing advantages such as enhanced visualization of the urinary sphincter,minimized urethral trauma,effective hemostasis,and reduced operative stress.The procedure utilizes specially designed instrumentation,including a large-caliber bipolar resectoscope(42 Fr),allowing the efficient removal of substantial adenoma tissue in fewer resection passes compared to traditional methods.Objectives:This article provides a comprehensive,step-by-step description of the STAR-P technique.The primary objective is to detail patient selection criteria,preoperative assessments,procedural steps including mini-open suprapubic access,specialized instrumentation usage,resection techniques,and postoperative management protocols.Highlighting technical considerations and procedural innovations aims to inform urologists about the potential benefits of STAR-P,particularly in patients at higher risk for urethral complications or those with large prostate volumes.By documenting the procedural intricacies and outcomes clearly and thoroughly,we seek to encourage informed adoption of STAR-P as an alternative,effective surgical approach for managing benign prostatic hyperplasia,thus contributing to the evolving landscape ofminimally invasive urological surgery.
基金supported by Tianjian advanced biomedical laboratory key research and development projectHenan Province Natural Science Foundation(Grant Number 242300421283)Major Science and Technology Project of Henan Province(221100310200)。
文摘Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.
基金supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
文摘Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.
文摘Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly cancer-associated fibroblasts(CAFs),as a critical determinant of disease behavior.CAFs constitute a heterogeneous population originating from fibroblasts,mesenchymal stem cells,endothelial cells,epithelial cells undergoing epithelial-mesenchymal transition(EMT),and adipose tissue.Through dynamic crosstalk with tumor,immune,endothelial,and adipocyte compartments,CAFs orchestrate oncogenic processes including tumor proliferation,invasion,immune evasion,extracellular matrix remodeling,angiogenesis,and metabolic reprogramming.This review comprehensively summarizes the cellular origins,phenotypic and functional heterogeneity,and spatial distribution of CAFs within the prostate TME.We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance,and critically evaluate emerging strategies to therapeutically target CAFmediated signaling,metabolic,and immune pathways.By integrating recent advances from single-cell and spatial transcriptomics(ST),our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.
基金supported by NIGMS(SC1GM140907 to G.-Y.L.)the Prostate Cancer Research Racial Disparity Grant from the Prostate Cancer Research(PCR)in the United Kingdom(grant reference[5001],to G.-Y.L.)the AU Medical Center,Inc.with a Grant/Contract Number CAU-AU Partnership-Kavuri-Liou and by NIMHDsupported Research Capacity Core at CAU(U54MD007590)。
基金supported by the funding of Chinese Scholarship Council(No.202206240086)。
文摘Objective:To identify chromatin regulators(CRs)-based molecular subtypes and risk scores for accurately predicting biochemical recurrence(BCR)after radical prostatectomy(RAP)in prostate cancer(PCa)patients.Methods:Differentially expressed genes(DEGs)between tumor and normal samples from The Cancer Genome Atlas(TCGA)and gene expression omnibus(GEO)databases were intersected with CR-related and prognostic genes.Consensus clustering,risk score analysis,functional analysis,immune microenvironment,m6A,and heterogeneity assessments were performed using R software.In vitro validation used DU145 and C42B PCa cell lines.Topoisomerase II alpha(TOP2A)was knocked down via si RNA.Assays included CCK-8 proliferation,colony formation,transwell migration/invasion,wound healing,and western blotting(WB)for pathway validation.Results:TOP2A and peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PPARGC1A)defined molecular subtypes and a risk score in TCGA,validated in a GEO dataset.Cluster 2 exhibited significantly shorter BCR-free survival vs.cluster 1 in TCGA[hazard ratio(HR):2.21;95%confidence interval(95%CI):1.32-3.73;P=0.003],GEO(HR:2.05;95%CI:1.05-4.02;P=0.010),and MSKCC2010(HR:5.93;95%CI:1.96-17.87;P<0.001).Similar survival differences were observed between high-and low-risk groups(defined by the median risk score).Cluster 2 showed greater tumor heterogeneity and higher m6A gene expression.Gene set variation analysis(GSVA)revealed downregulated cell-cycle pathways in cluster 2,alongside suppressed tumor-infiltrating immune cells.TOP2A knockdown significantly impaired PCa cell proliferation,colony formation,migration,and invasion.Mechanistically,it suppressed phosphoinositide 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)pathway activation,reducing phosphorylated PI3K and AKT levels without altering total protein.Conclusions:TOP2A and PPARGC1A effectively stratify PCa subtypes for RAP patients.TOP2A drives malignant progression via the PI3K/AKT pathway.
文摘Objectives:Prostate cancer(PCa)is a highly prevalent male malignancy with limited efficacy in advanced stages.Dysregulated modulation of necroptosis was reported to be tightly correlated with PCa initiation and progression.Herein,we aimed to identify necroptosis-associated long non-coding RNAs(lncRNAs)and delineate their functional roles in PCa through an integrated approach combining bioinformatic analyses and in vitro experimental validation.Methods:RNA sequencing data and corresponding clinical information of PCa were downloaded from The Cancer Genome Atlas(TCGA).Differentially expressed necroptosis-related genes(NRGs)and lncRNAs were screened,and necroptosis activity was assessed by single-sample gene set enrichment analysis(ssGSEA).Weighted Gene Co-expression Network Analysis(WGCNA)identified necroptosis-related lncRNA modules,with key lncRNAs prioritized via Cox regression.Clinical correlation analyses and in vitro experiments validated the function of the key lncRNA LINC00595.Results:A total of 50 differentially expressed NRGs were identified,among which pro-necroptotic genes exhibited pronounced downregulation,while anti-necroptotic genes were significantly upregulated.Consistently,ssGSEA confirmed reduced necroptosis activity in PCa.WGCNA further identified 13 core necroptosis-related lncRNAs(NRlncRNAs),with Cox regression analysis pinpointing LINC00595 and LINC00908 as the top prognostic candidates.Both lncRNAs were downregulated in PCa,with low expression correlating with advanced T stage,lymph node metastasis,and poor prognosis.Functional experiments demonstrated that LINC00595 overexpression inhibited PCa cell proliferation,migration,and invasion,and enhanced necroptosis.Conclusions:Collectively,our findings identified LINC00595 and LINC00908 as novel regulators of necroptosis in PCa.Specifically,LINC00595 exerted tumor-suppressive effects by enhancing necroptosis,holding potential as prognostic biomarkers and therapeutic targets.
文摘Objective:Androgen receptor(AR)signaling is a central driver of prostate cancer progression,yet the metabolic and transcriptional mechanisms regulating AR expression remain incompletely characterized.This study investigated whether the immunoproteasome inhibitor ONX-0914 suppresses hormone-sensitive prostate cancer(HSPC)through metabolic modulation of AR and aimed to identify the transcriptional mediator involved.Methods:HSPC and castration-resistant prostate cancer models were used to evaluate the effects of ONX-0914 on cell proliferation,invasion,migration,and epithelial-mesenchymal transition.Xenograft assays,bioinformatic screening,and analyses of O-GlcNAcylation and protein stability were performed,together with quantitative polymerase chain reaction(qPCR)and Western blotting.Results:ONX-0914 markedly suppressed hormone-sensitive prostate cancer(HSPC)progression through both LMP7-dependent and LMP7-independent mechanisms.Mechanistically,ONX-0914 activated the hexosamine biosynthetic pathway and enhanced global O-GlcNAcylation,leading to stabilization of the transcriptional repressor Transcription factor 7-like 1(TCF7L1)and consequent suppression of androgen receptor(AR)expression.Functionally,activation of the O-GlcNAcylation-TCF7L1 axis inhibited cell proliferation,invasion,migration,and epithelial-mesenchymal transition in vitro.In vivo,TCF7L1 overexpression,particularly under conditions of enhanced O-GlcNAcylation,significantly suppressed tumor growth and AR expression.Conclusion:This study identifies a novel ONX-0914/HBP/TCF7L1 O-GlcNAcylation axis that metabolically stabilizes TCF7L1,leading to repression of AR signaling and inhibition of HSPC progression.These findings reveal a previously unrecognized metabolic-transcriptional regulatory mechanism and highlight TCF7L1 O-GlcNAcylation as a potential therapeutic target in AR-dependent prostate cancer.
基金supported by the Clinical Research of Tianjin Medical University(No.2018kylc004)the Medical Science Research Project of Hebei(No.20250372).
文摘Objective:Prostate cancer is the second most common fatal cancer in men.Identifying new biological therapeutic targets is crucial to effectively improve the prognosis of prostate cancer patients.Ovarian tumor family deubiquitinase 4(OTUD4)is a member of the ovarian tumor-associated protease domain(OTUDs)family.Although previous studies have shown that the expression and function of OTUD4 vary across different tumors,its role in prostate cancer remains unknown.The aim of this study is to explore new therapeutic targets and diagnostic markers for prostate cancer and investigate their mechanisms of action.Methods:Cell culture,Cell Counting Kit-8(CCK-8)assay,colony formation assay,Transwell assay,5-Ethynyl-2′-deoxyuridine(EdU)assay,immunofluorescence,Western blot,Quantitative real-time PCR(qRT-PCR),protein mass spectrometry,nude mouse xenograft models,immunohistochemistry(IHC),and hematoxylin and eosin(H&E)staining were utilized.Results:We found that OTUD4 expression was reduced in prostate cancer and negatively correlated with poor prognosis in both in vivo and in vitro experiments.Subsequent mechanistic studies revealed that OTUD4 directly inhibits the degradation of myosin-9(MYH9)protein via deubiquitination.Although MYH9 has been previously reported to act as a tumor suppressor in prostate cancer,no experimental evidence had demonstrated that MYH9 inhibits prostate cancer growth.Our results indicate that MYH9 overexpression effectively suppresses prostate cancer through interactions with cell adhesion molecules.Conclusion:Collectively,these results suggest that OTUD4 functions as a tumor suppressor in prostate cancer.Specifically,OTUD4 inhibits MYH9 degradation via deubiquitination,thereby enabling MYH9-mediated suppression of prostate cancer.
文摘Radical prostatectomy is a commonly used surgical method in cases of localized prostate cancer.In recent years,with the advent of new medical technologies and surgical techniques,the evolution of radical prostatectomy has revolutionized,especially in robot-assisted radical prostatectomy(RARP).The evolution of surgical approaches for radical prostatectomy has occurred in three stages:open surgery,laparoscopic intervention,and robot-assisted surgery.Regarding the functional recovery of patients who underwent laparoscopic radical prostatectomy or RARP,with the improvement of disease conditions,oncological prognosis of patients was not compromised.Particularly,RARP boasts distinguished novel techniques and approaches for maintaining urinary continence and sexual function in the short-and long-term.In addition,studies in the last two decades have shown its correlation with decreasing postoperative morbidity.In this paper,the available literatures related to the surgical approaches ranging from open surgery to RARP were reviewed,the superiority of any novel procedure was analyzed,and the advantages and disadvantages among the three modalities were compared,hoping to provide guidance to urologists when considering surgical approaches in the treatment of localized prostate cancer.
文摘In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen （PSA） testing remains very low compared with Western countries, and the benefits of population-based screening remain unclear. This review describes the current status of population screening and diagnosis for prostate cancer in Japan and discusses the efficacy of population screening for the Asian population. Since the 1990s, screening systems have been administered by each municipal government in Japan, and decreases in the prostate cancer mortality rate are expected in some regions where the exposure rate to PSA screening has increased markedly. A population-based screening cohort revealed that the proportion of metastatic disease in cancer detected by screening gradually decreased according to the increased exposure rate, and a decreasing trend in the proportion of cancer with high serum PSA levels after population screening was started. The prognosis of the prostate cancer detected by population screening was demonstrated to be more favorable than those diagnosed outside of the population screening. Recent results in screening cohorts demonstrated the efficacy of PSA. These recent evidences regarding population-based screening in Japan may contribute to establishing the optimal prostate cancer screeninK system in Asian individuals.
基金supported by the Interdepartmental Research Project of Peking University First Hospital(No.2023IR27 to Liu Y)the Scientific Research Seed Fund of Peking University First Hospital(No.2023SF40 to Qiu J)+3 种基金the High Quality Clinical Research Project of Peking University First Hospital(No.2022CR75 to Gong K)the Beijing Natural Science Foundation(No.QY23068 to Deng R)the National Natural Science Foundation of China(No.82141103,No.82172617,and No.81872081 to Gong K)the Capital’s Funds for Health Improvement and Research(No.2022-2-4074 to Gong K).
文摘Objective:To explore clinicopathological predictors of adverse pathological changes(APCs)(upgrading,upstaging,and positive surgical margin[PSM])after robot-assisted radical prostatectomy(RARP)in clinical tumor stage 2c(cT2c)prostate cancer(PCa)patients.Methods:From January 2018 to December 2022,cT2cN0M0 PCa patients who underwent prostate biopsies and subsequent RARP at the Peking University First Hospital with an interval between biopsy and RARP of ≤90 days were included.Univariable and stepwise multivariable logistic regression analyses were performed to identify independent risk factors associated with APCs.Nomograms were constructed based on these predictive models.The performance of the nomograms was evaluated by receiver operating characteristic curves,decision curve analyses,and calibration plots.Results:A total of 423 eligible cT2cN0M0 PCa patients were included.The rates of upgrading,upstaging,and PSM in our cohortwere 33%,51%,and 35%,respectively.The stepwise multivariate logistic analysis suggested that PSA density and the percentage of positive cores in systematic biopsy were significantly associated with the occurrence of APCs.The score of the Prostate Imaging Reporting and Data System,PSA density,and the International Society of Urological Pathology grade group(IGG)of needle-biopsy specimens(or clinical IGG[cIGG])were significantly associated with upgrading.The PSA density,percentage of positive cores in systematic biopsy,and largest tumor percentage in all cores of each patient(LTP)were significantly associated with upstaging.The PSA density and LTP were significantly associatedwith the PSM.Based on these results,four nomogramswere developed.Receiver operating characteristic curves,decision curve analyses,and calibration plots implied that the nomograms exhibited excellent accuracy.Conclusion:The predictive models we developed could help to identify high-risk PCa early,and optimize clinical decisions of cT2cN0M0 PCa patients.
文摘Background:Prostate cancer is a common malignancy,with many men on active surveillance for localized,low-risk disease also experiencing lower urinary tract symptoms(LUTS)from benign prostatic hyperplasia(BPH).Water Vapor Thermal Therapy(WVTT)is a minimally invasive BPH treatment,but its safety and efficacy in this setting are unclear.Case Description:We report three men with localized PCa on active surveillance who underwent WVTT for LUTS.Conclusions:WVTT appears safe and potentially effective in treating LUTS,especially in those with lower-risk disease and smaller prostate volumes.Further research is needed to confirm safety,efficacy,and optimal patient selection.
