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...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.Start-ing from the perspective of RNA sequencing technology,this review outlined the signifcance 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.展开更多
Prostate cancer(PCa)is one of the most common malignant tumors in the male genitourinary system,ranking second in incidence worldwide.Traditional Chinese medicine(TCM),as an important component of complementary and al...Prostate cancer(PCa)is one of the most common malignant tumors in the male genitourinary system,ranking second in incidence worldwide.Traditional Chinese medicine(TCM),as an important component of complementary and alternative medicine,shows unique advantages in cancer treatment.Chinese herbal medicine is usually composed of multiple ingredients and involves multiple signaling pathways,which showed function of inducing apoptosis of cancer cells,arresting the cell cycle,inhibiting invasion and metastasis,reducing drug resistance,and regulating immune function.Physical therapy is also an important treatment of TCM.Currently,Physical therapy such as acupuncture or Tai Chi and Qigong are gaining increased recognition in the management of PCa,particularly in addressing issues like urinary incontinence and bone metastasis-related pain.This article reviews the TCM treatment and therapy of PCa,in order to provide new research avenues and treatment options for the treatment of PCa with TCM and improve the quality of life of patients.展开更多
Background:Transmembrane emp24 trafficking protein 3(TMED3)is associated with the development of several tumors;however,whether TMED3 regulates the progression of prostate cancer remains unclear.Materials and Methods:...Background:Transmembrane emp24 trafficking protein 3(TMED3)is associated with the development of several tumors;however,whether TMED3 regulates the progression of prostate cancer remains unclear.Materials and Methods:Short hairpin RNA was performed to repress TMED3 in prostate cancer cells(DU145 cells)and in a prostate cancer mice model to determine its function in prostate cancer in vitro and in vivo.Results:In the present study,we found that TMED3 was highly expressed in prostate cancer cells.In vitro,shTMED3 treatment suppressed the proliferation,invasion,and migration and promoted the apoptosis of DU145 cells.Additionally,the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed a strong correlation between TMED3 and forkhead box O transcription factor(FOXO)pathway.Furthermore,TMED3 inhibition efficiently decreased FOXO1a and FOXO3a phosphorylation.In vivo,TMED3 downregulation suppressed the apoptosis,growth,and metastasis of prostate cancer cells via FOXO1a and FOXO3a.Conclusion:The present findings show that TMED3 participates in the regulation of prostate cancer progression via FOXO1a and FOXO3a phosphorylation,thereby revealing a novel mechanism underlying prostate cancer development and suggesting that TMED3 inhibition may serve as a novel strategy for prostate cancer treatment.展开更多
Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with near...Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with nearly 400,000 associated deaths1. Notably, the incidence of PC in China has increased substantially compared to the global average2.展开更多
BACKGROUND Vitamin D deficiency has been associated with prostate cancer,particularly in ethnic minorities.Patients with prostate cancer may still be deficient even in areas of high sun exposure.Although androgen depr...BACKGROUND Vitamin D deficiency has been associated with prostate cancer,particularly in ethnic minorities.Patients with prostate cancer may still be deficient even in areas of high sun exposure.Although androgen deprivation therapy(ADT)is well documented to affect bone health,its impact on vitamin D levels is still uncertain.This study investigates the subgroups of prostate cancer patients most associated with vitamin D deficiency and ADT’s relation to this.AIM To examine how prevalent vitamin D deficiency is among prostate cancer patients in a sun-rich environment,with focus on differences by race and disease stage.It also assessed whether ADT is associated with changes in vitamin D levels.METHODS Prostate cancer patients treated at Chao Family Comprehensive Cancer Center between 2014-2024 were retrospectively studied with regards to vitamin D levels across racial groups,disease stages,and ADT exposure.Changes in vitamin D levels pre-and post-ADT over 24 months were assessed by statistical methods including paired t-tests.RESULTS Among 120 patients(mean age:74 years,mean body mass index:27.6 kg/m^(2)),African American(33.3%)and Hispanic(31.8%)patients had the greatest prevalence of vitamin D deficiency(<20 ng/mL).With a 28.6%deficit rate,metastatic castration-resistant prostate cancer had the highest prevalence rates of deficiency.There was no significant difference between pre-and post-ADT vitamin D levels(P=0.45).CONCLUSION Vitamin D deficiency is common in prostate cancer patients,especially racial minorities and those with advanced disease,despite residing in an area with high sun exposure.ADT does not significantly impact vitamin D levels in the short term.Routine screening and supplementation should be considered in these high-risk groups.展开更多
Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regula...Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regulate gene transcription via nuclear receptors TRα/β,modulating proliferation,apoptosis,and AR signaling,while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K-Akt signaling,driving metabolic reprogramming,migration,and angiogenesis.Local DIO enzymes fine-tune T3/T4 levels,with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion.Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk,whereas experimental models show inconsistent effects,reflecting regulation by hormone levels,receptor distribution,and tumor molecular features.Bibliometric analyses reveal a shift from epidemiological studies to molecular,immune,and metabolic mechanistic research,though clinical translation remains limited.This review synthesizes current knowledge on THs in PCa,highlighting mechanistic insights,evidence gaps,and future directions,aiming to inform early detection,stratification,and therapeutic strategies.展开更多
Emerging biomarkers,such as tumor mutational burden and circulating tumor DNA(ctDNA),offer promising tools for identifying patients with prostate cancer who may benefit from immune checkpoint inhibitor therapy.This re...Emerging biomarkers,such as tumor mutational burden and circulating tumor DNA(ctDNA),offer promising tools for identifying patients with prostate cancer who may benefit from immune checkpoint inhibitor therapy.This report describes an exceptional response to pembrolizumab in a patient with a microsatellite stability metastatic castration-resistant prostate cancer and ultrahigh tumor mutational burden.Additionally,this case further emphasizes the utility of ctDNA for monitoring molecular residual disease in patients whose disease burden is not adequately reflected by prostate-specific antigen levels and supports the use of ctDNA as a biomarker for personalized treat-ment monitoring and guiding treatment de-escalation.展开更多
Prostate cancer is a significant global health issue with inflammation emerging as a critical driver of progression.The prostate tumor microenvironment(TME)is comprised of tumor cells,mesenchymal stem cells,immune cel...Prostate cancer is a significant global health issue with inflammation emerging as a critical driver of progression.The prostate tumor microenvironment(TME)is comprised of tumor cells,mesenchymal stem cells,immune cells,cancer-associated fibroblasts,adipocytes,and the extracellular matrix.All of these TME components interact via soluble factors,such as growth factors,cytokines,and chemokines.These interactions remodel the TME and drive inflammation and tumor progression.Prolonged inflammation leads to dysregulated activation and infiltration of immune cells in the TME.This process maintains an immunosuppressive environment and facilitates epithelial-to-mesenchymal transition,migration,and invasion.Chronic inflammation causes inflammatory mediators to enter the circulation over time,as evidenced by systemic biomarkers,such as the systemic immune-inflammation index,which links inflammation to disease severity.Interactions between the prostate gland and adipose tissues further exacerbate systemic inflammation.Inflammation in the prostate gland confers resistance to therapy,primes distant metastatic niches,and promotes metastatic spread,resulting in poor clinical outcomes.Therapeutic strategies,such as anti-inflammatory agents and immunotherapies,hold promise in mitigating disease burden.This review explored the immune landscape of systemic inflammation in prostate cancer,discussed the role of the immune landscape in resistance to therapy and metastasis,and offered insights into potential interventions for targeting inflammation to limit prostate cancer burden.展开更多
The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research...The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.展开更多
BACKGROUND The development of prostate cancer(PC)frequently intensifies negative emotional states,such as anxiety and depression,which compromise the effectiveness of radical surgery and reduce treatment adherence.In ...BACKGROUND The development of prostate cancer(PC)frequently intensifies negative emotional states,such as anxiety and depression,which compromise the effectiveness of radical surgery and reduce treatment adherence.In this study,we hypothesized that psychological resilience plays a crucial role in this process and explored its impact.AIM To investigate the association of resilience with anxiety and depression in patients with PC and to analyze the influencing factors.METHODS We selected 147 patients with PC who visited Qingdao Traditional Chinese Medicine Hospital from January 2022 to June 2024.The resilience scores of patients with PC were assessed using the Connor-Davidson Resilience Scale(CDRISC)from the tenacity,self-improvement,and optimism dimensions.Based on the total CD-RISC score,patients were categorized into groups A(total CD-RISC score>63 points,n=69)and B(total CD-RISC score≤63 points,n=78)for comparative analysis of anxiety[Hamilton Anxiety Rating Scale(HAMA)],depression[Hamilton Depression Rating Scale(HAMD)],sexual function[International Index of Erectile Function-5(IIEF-5)and Sexual Life Quality Questionnaire-Quality of Life(SLQQ-QOL)],and quality of life[the EORTC Core Quality of Life Question naire(QLQ-C30)].The association between CD-RISC and the above indicators was analyzed with Spearman correlation coefficients,and the influencing factors of resilience in patients with PC were identified with binary logistic regression.RESULTS Group A demonstrated statistically lower HAMA and HAMD scores and markedly higher scores of IIEF-5,SLQQQOL,and various QLQ-C30 aspects.Correlation analysis revealed that CD-RISC was significantly negatively correlated with HAMA and HAMD scores and significantly positively correlated with IIEF-5,SLQQ-QOL,and QLQ-C30 total scores.Binary logistic regression analysis revealed educational and per capita monthly household income levels as significant influencing factors of resilience in patients with PC.CONCLUSION Our results indicate a significant correlation of resilience with anxiety and depression in patients with PC.The milder the anxiety and depression emotions in patients,the higher their resilience.Further,assisting patients with PC to improve their educational and per capita monthly household income levels will help their resilience to some extent.展开更多
Purpose:While the mental health impact of a prostate cancer diagnosis,including low-risk prostate cancer,is well-documented,the effect of pre-existing anxiety and/or depression on adherence to active surveillance prot...Purpose:While the mental health impact of a prostate cancer diagnosis,including low-risk prostate cancer,is well-documented,the effect of pre-existing anxiety and/or depression on adherence to active surveillance protocols in low-risk prostate cancer patients remains unclear.This study assessed the association between prior anxiety and/or depression and active surveillance adherence in men with low-risk prostate cancer.Methods:We conducted a retrospective,multicenter study involving 426 men diagnosed with low-risk prostate cancer who were recommended active surveillance as the primary management strategy.Active surveillance adherence was defined by completion of both a prostate-specific antigen test and a prostate biopsy within 18 months of diagnosis.Premature treatment was identified as definitive treatment,either through radiation therapy or radical prostatectomy.Results:Men with a prior mental health diagnosis were significantly less likely to adhere to active surveillance than those without such a diagnosis(27.6%vs.49.5%,p=0.006).These individuals had lower adherence rates for prostate-specific testing(58.6%vs.73.4%)and biopsy(27.6%vs.50.0%)and were more likely to abandon active surveillance in favor of immediate treatment(39.7%vs.25.0%,p=0.005).No significant differences were observed between patients with both anxiety and depression versus those with a single diagnosis.Conclusions:Pre-existing anxiety and/or depression is associated with reduced active surveillance adherence and a greater likelihood of premature treatment in men with low-risk prostate cancer.These findings highlight the importance of addressing psychiatric factors in lowrisk prostate cancer management and suggest avenues for future research.展开更多
Xiaoaiping(XAP)Injection demonstrates the anti-prostate cancer(PCa)effects,yet the underlying mechanism remains unclear.This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action.PCa...Xiaoaiping(XAP)Injection demonstrates the anti-prostate cancer(PCa)effects,yet the underlying mechanism remains unclear.This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action.PCa cell proliferation was evaluated using a cell counting kit-8(CCK-8)assay.Cell apoptosis was assessed through Hoechst staining and Western blotting assays.Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells.To further validate potential key genes and important pathways,a series of assays were conducted,including acridine orange(AO)staining,transmission electron microscopy,and immunofluorescence assays.The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model.Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines.In C4-2 and prostate cancer cell line-3(PC3)cells,XAP induced cellular apoptosis,evidenced by reduced B-cell lymphoma 2(Bcl-2)levels and elevated Bcl-2-associated X(Bax)levels.Proteomic,immunofluorescence,and quantitative reverse transcription-polymerase chain reaction(q RT-PCR)investigations revealed a strong correlation between forkhead box O3a(FoxO3a)autophagic degradation and the anti-PCa action of XAP.XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5(Atg5)/autophagy-related protein 12(Atg12)and enhancing FoxO3a expression and nuclear translocation.Furthermore,XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue.These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation,potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.展开更多
Background:Transrectal(TR)and transperineal(TP)biopsies are commonly used methods for diagnosing prostate cancer.However,their comparative effectiveness in conjunction with machine learning(ML)techniques remains under...Background:Transrectal(TR)and transperineal(TP)biopsies are commonly used methods for diagnosing prostate cancer.However,their comparative effectiveness in conjunction with machine learning(ML)techniques remains underexplored.This study aimed to evaluate the predictive accuracy of ML algorithms in detecting prostate cancer using data derived from TR and TP biopsies.Methods:The clinical records of patients who underwent prostate biopsy at King Saud University Medical City and King Faisal Specialist Hospital and Research Centerin Riyadh,Saudi Arabia,between 2018 and 2025 were analyzed.Data were used to train and testMLmodels,including eXtreme Gradient Boosting(XGBoost),Decision Tree,Random Forest,and Extra Trees.Results:The two datasets are comparable.The models demonstrated exceptional performance,achieving accuracies of up to 96.49%and 95.56%on TP and TR biopsy datasets,respectively.The area under the curve(AUC)values were also high,reaching 0.9988 for TP and 0.9903 for TR biopsy predictions.Conclusion:These findings highlight the potential of MLto enhance the diagnostic accuracy of prostate cancer detection irrespective of the biopsy method.However,TP biopsy data showed marginally higher accuracy,possibly because of the lower risk of contamination.While ML holds great promise for transforming prostate cancer care,further research is needed to address limitations.Collaboration between clinicians,data scientists,and researchers is crucial to ensure the clinical relevance and interpretability of ML models.展开更多
Prostate cancer (PCa) is the second most common type of cancer among men worldwide and one of the leading causes of cancer-related deaths. According to data from the World Health Organization (WHO), this cancer causes...Prostate cancer (PCa) is the second most common type of cancer among men worldwide and one of the leading causes of cancer-related deaths. According to data from the World Health Organization (WHO), this cancer causes hundreds of thousands of new cases and tens of thousands of male deaths globally each year. The incidence of PCa varies across different regions and populations, generally being higher in developed countries. This disparity may be attributed to lifestyle factors and the widespread availability of screening and diagnostic technologies. Prostate-specific membrane antigen (PSMA) is a membrane-bound enzyme predominantly expressed in prostate tissue and PCa cells, with lower expression in normal tissues. This high expression makes PSMA a critical target for the diagnosis and treatment of PCa, particularly in the field of molecular imaging and radiopharmaceutical therapy. Recently, various studies have emerged on radiopharmaceuticals developed based on PSMA ligands, which can be used to specifically identify and locate PCa cells. Research on the radiomics of these novel drugs has also been updated. This article will discuss the role and limitations of PSMA PET in the diagnosis and management of PCa treatment.展开更多
As a practicing anatomic pathologist specialized in urologic pathology,a vast difference may be observed between what pathologists designate as neuroendocrine(or small cell)carcinoma of the prostate,and what clinician...As a practicing anatomic pathologist specialized in urologic pathology,a vast difference may be observed between what pathologists designate as neuroendocrine(or small cell)carcinoma of the prostate,and what clinicians or basic scientists define as such.展开更多
Prostate cancer(PCa)is characterized by high incidence and propensity for easy metastasis,presenting significant challenges in clinical diagnosis and treatment.Tumor microenvironment(TME)-responsive nanomaterials prov...Prostate cancer(PCa)is characterized by high incidence and propensity for easy metastasis,presenting significant challenges in clinical diagnosis and treatment.Tumor microenvironment(TME)-responsive nanomaterials provide a promising prospect for imaging-guided precision therapy.Considering that tumor-derived alkaline phosphatase(ALP)is over-expressed in metastatic PCa,it makes a great chance to develop a theranostics system with ALP responsive in the TME.Herein,an ALP-responsive aggregationinduced emission luminogens(AIEgens)nanoprobe AMNF self-assembly was designed for enhancing the diagnosis and treatment of metastatic PCa.The nanoprobe exhibited self-aggregation in the presence of ALP resulted in aggregation-induced fluorescence,and enhanced accumulation and prolonged retention period at the tumor site.In terms of detection,the fluorescence(FL)/computed tomography(CT)/magnetic resonance(MR)multi-mode imaging effect of nanoprobe was significantly improved post-aggregation,enabling precise diagnosis through the amalgamation of multiple imaging modes.Enhanced CT/MR imaging can achieve assist preoperative tumor diagnosis,and enhanced FL imaging technology can achieve“intraoperative visual navigation”,showing its potential application value in clinical tumor detection and surgical guidance.In terms of treatment,AMNF showed strong absorption in the near infrared region after aggregation,which improved the photothermal treatment effect.Overall,our work developed an effective aggregation-enhanced theranostic strategy for ALP-related cancers.展开更多
Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most...Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most important target for prostate cancer treatment.Current USA Food and Drug Administration(FDA)-approved AR inhibitors target the ligand-binding domain(LBD)and have exhibited efficacy in prostate cancer patients,particularly when used in combination with androgen deprivation therapy.Unfortunately,patients treated with the currently approved AR-targeting agents develop resistance and relapse with castration-resistant prostate cancer(CRPC).The major mechanism leading to CRPC involves reactivation of AR signaling mainly through AR gene amplification,mutation,and/or splice variants.To effectively inhibit the reactivated AR signaling,new approaches to target AR are being actively explored.These new approaches include novel small molecule inhibitors targeting various domains of AR and agents that can degrade AR.The present review provides a summary of the existing FDA-approved AR antagonists and the current development of some of the AR targeting agents.展开更多
One in every eight men in the US is diagnosed with prostate cancer,making it the most common cancer in men.Gleason grading is one of the most essential diagnostic and prognostic factors for planning the treatment of p...One in every eight men in the US is diagnosed with prostate cancer,making it the most common cancer in men.Gleason grading is one of the most essential diagnostic and prognostic factors for planning the treatment of prostate cancer patients.Traditionally,urological pathologists perform the grading by scoring the morphological pattern,known as the Gleason pattern,in histopathology images.However,thismanual grading is highly subjective,suffers intra-and inter-pathologist variability and lacks reproducibility.An automated grading system could be more efficient,with no subjectivity and higher accuracy and reproducibility.Automated methods presented previously failed to achieve sufficient accuracy,lacked reproducibility and depended on high-resolution images such as 40×.This paper proposes an automated Gleason grading method,ProGENET,to accurately predict the grade using low-resolution images such as 10×.This method first divides the patient’s histopathology whole slide image(WSI)into patches.Then,it detects artifacts and tissue-less regions and predicts the patch-wise grade using an ensemble network of CNN and transformer models.The proposed method adapted the International Society of Urological Pathology(ISUP)grading system and achieved 90.8%accuracy in classifying the patches into healthy and Gleason grades 1 through 5 using 10×WSI,outperforming the state-of-the-art accuracy by 27%.Finally,the patient’s grade was determined by combining the patch-wise results.The method was also demonstrated for 4−class grading and binary classification of prostate cancer,achieving 93.0%and 99.6%accuracy,respectively.The reproducibility was over 90%.Since the proposedmethod determined the grades with higher accuracy and reproducibility using low-resolution images,it is more reliable and effective than existing methods and can potentially improve subsequent therapy decisions.展开更多
The choice of biopsy method is critical in diagnosing prostate cancer(PCa).This retrospective cohort study compared systematic biopsy(SB)or cognitive fusion-targeted biopsy combined with SB(CB)in detecting PCa and cli...The choice of biopsy method is critical in diagnosing prostate cancer(PCa).This retrospective cohort study compared systematic biopsy(SB)or cognitive fusion-targeted biopsy combined with SB(CB)in detecting PCa and clinically significant prostate cancer(csPCa).Data from 2572 men who underwent either SB or CB in Fudan University Shanghai Cancer Center(Shanghai,China)between January 2019 and December 2023 were analyzed.Propensity score matching(PSM)was used to balance baseline characteristics,and detection rates were compared before and after PSM.Subgroup analyses based on prostate-specific antigen(PSA)levels and Prostate Imaging-Reporting and Data System(PI-RADS)scores were performed.Primary and secondary outcomes were the detection rates of PCa and csPCa,respectively.Of 2572 men,1778 were included in the PSM analysis.Before PSM,CB had higher detection rates for both PCa(62.9%vs 52.4%,odds ratio[OR]:1.54,P<0.001)and csPCa(54.9%vs 43.3%,OR:1.60,P<0.001)compared to SB.After PSM,CB remained superior in detecting PCa(63.1%vs 47.9%,OR:1.86,P<0.001)and csPCa(55.0%vs 38.2%,OR:1.98,P<0.001).In patients with PSA 4–12 ng ml−1(>4 ng ml-1 and≤12 ng ml-1,which is also applicable to the following text),CB detected more PCa(59.8%vs 40.7%,OR:2.17,P<0.001)and csPCa(48.1%vs 27.7%,OR:2.42,P<0.001).CB also showed superior csPCa detection in those with PI-RADS 3 lesions(32.1%vs 18.0%,OR:2.15,P=0.038).Overall,CB significantly improves PCa and csPCa detection,especially in patients with PSA 4–12 ng ml−1 or PI-RADS 3 lesions.展开更多
Objective:Prostate cancer(PCa)exhibits significant genomic differences between Western and Asian populations.This study aimed to design a predictive model applicable across diverse populations while selecting a limite...Objective:Prostate cancer(PCa)exhibits significant genomic differences between Western and Asian populations.This study aimed to design a predictive model applicable across diverse populations while selecting a limited set of genes suitable for clinical implementation.Methods:We utilized an integrated dataset of 1360 whole-exome and whole-genome sequences from Chinese and Western PCa cohorts to develop and evaluate the model.External validation was conducted using an independent cohort of patients.A graph neural network architecture,termed the pathway-aware multi-layered hierarchical network-Western and Asian(P-NETwa),was developed and trained on combined genomic profiles from Chinese and Western cohorts.The model employed a multilayer perceptron(MLP)to identify key signature genes from multiomics data,enabling precise prediction of PCa metastasis.Results:The model achieved an accuracy of 0.87 and an F1-score of 0.85 on Western population datasets.The application of integrated Chinese and Western population data improved the accuracy to 0.88,achieving an F1-score of 0.75.The analysis identified 18 signature genes implicated in PCa progression,including established markers(AR and TP53)and novel candidates(MUC16,MUC4,and ASB12).For clinical adoption,the model was optimized for commercially available gene panels while maintaining high classification accuracy.Additionally,a user-friendly web interface was developed to facilitate real-time prediction of primary versus metastatic status using the pre-trained P-NETwa-MLP model.Conclusion:The P-NETwa-MLP model integrates a query system that allows for efficient retrieval of prediction outcomes and associated genomic signatures via sample ID,enhancing its potential for seamless integration into clinical workflows.展开更多
基金Chinese Scholarship Council(202206240086)National Natural Science Foundation of China(81974099,82170785,81974098,82170784)+4 种基金National Key Research and Development Program of China(2021YFC2009303)programs from Science and Technology Department of Sichuan Province(2021YFH0172)Young Investigator Award of Sichuan University 2017(2017SCU04A17)Technology Innovation Research and Development Project of Chengdu Science and Technology Bureau(2019-YF05-00296-SN)Sichuan University-Panzhihua science and technology cooperation special fund(2020CDPZH-4).
文摘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.Start-ing from the perspective of RNA sequencing technology,this review outlined the signifcance 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.
基金supported by China Postdoctoral Science Foundation(2022M722674)Peixian Science and Technology Plan Project(P202410)Xuzhou Medical Reserve Talents Project(XWRCHT20220009).
文摘Prostate cancer(PCa)is one of the most common malignant tumors in the male genitourinary system,ranking second in incidence worldwide.Traditional Chinese medicine(TCM),as an important component of complementary and alternative medicine,shows unique advantages in cancer treatment.Chinese herbal medicine is usually composed of multiple ingredients and involves multiple signaling pathways,which showed function of inducing apoptosis of cancer cells,arresting the cell cycle,inhibiting invasion and metastasis,reducing drug resistance,and regulating immune function.Physical therapy is also an important treatment of TCM.Currently,Physical therapy such as acupuncture or Tai Chi and Qigong are gaining increased recognition in the management of PCa,particularly in addressing issues like urinary incontinence and bone metastasis-related pain.This article reviews the TCM treatment and therapy of PCa,in order to provide new research avenues and treatment options for the treatment of PCa with TCM and improve the quality of life of patients.
基金supported by Guangxi Medical and Health Appropriate Technology Development and Promotion Application Project(S2022022).
文摘Background:Transmembrane emp24 trafficking protein 3(TMED3)is associated with the development of several tumors;however,whether TMED3 regulates the progression of prostate cancer remains unclear.Materials and Methods:Short hairpin RNA was performed to repress TMED3 in prostate cancer cells(DU145 cells)and in a prostate cancer mice model to determine its function in prostate cancer in vitro and in vivo.Results:In the present study,we found that TMED3 was highly expressed in prostate cancer cells.In vitro,shTMED3 treatment suppressed the proliferation,invasion,and migration and promoted the apoptosis of DU145 cells.Additionally,the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed a strong correlation between TMED3 and forkhead box O transcription factor(FOXO)pathway.Furthermore,TMED3 inhibition efficiently decreased FOXO1a and FOXO3a phosphorylation.In vivo,TMED3 downregulation suppressed the apoptosis,growth,and metastasis of prostate cancer cells via FOXO1a and FOXO3a.Conclusion:The present findings show that TMED3 participates in the regulation of prostate cancer progression via FOXO1a and FOXO3a phosphorylation,thereby revealing a novel mechanism underlying prostate cancer development and suggesting that TMED3 inhibition may serve as a novel strategy for prostate cancer treatment.
文摘Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with nearly 400,000 associated deaths1. Notably, the incidence of PC in China has increased substantially compared to the global average2.
文摘BACKGROUND Vitamin D deficiency has been associated with prostate cancer,particularly in ethnic minorities.Patients with prostate cancer may still be deficient even in areas of high sun exposure.Although androgen deprivation therapy(ADT)is well documented to affect bone health,its impact on vitamin D levels is still uncertain.This study investigates the subgroups of prostate cancer patients most associated with vitamin D deficiency and ADT’s relation to this.AIM To examine how prevalent vitamin D deficiency is among prostate cancer patients in a sun-rich environment,with focus on differences by race and disease stage.It also assessed whether ADT is associated with changes in vitamin D levels.METHODS Prostate cancer patients treated at Chao Family Comprehensive Cancer Center between 2014-2024 were retrospectively studied with regards to vitamin D levels across racial groups,disease stages,and ADT exposure.Changes in vitamin D levels pre-and post-ADT over 24 months were assessed by statistical methods including paired t-tests.RESULTS Among 120 patients(mean age:74 years,mean body mass index:27.6 kg/m^(2)),African American(33.3%)and Hispanic(31.8%)patients had the greatest prevalence of vitamin D deficiency(<20 ng/mL).With a 28.6%deficit rate,metastatic castration-resistant prostate cancer had the highest prevalence rates of deficiency.There was no significant difference between pre-and post-ADT vitamin D levels(P=0.45).CONCLUSION Vitamin D deficiency is common in prostate cancer patients,especially racial minorities and those with advanced disease,despite residing in an area with high sun exposure.ADT does not significantly impact vitamin D levels in the short term.Routine screening and supplementation should be considered in these high-risk groups.
基金Guangzhou Medical and Health Science and Technology Project(Project No.:20231A011103)General projects of Guangzhou municipal Science and Technology Bureau(Project No.:2023A04J0598)Guangdong Basic and Applied Basic Research Foundation(Project No.:2022A1515111122)。
文摘Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regulate gene transcription via nuclear receptors TRα/β,modulating proliferation,apoptosis,and AR signaling,while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K-Akt signaling,driving metabolic reprogramming,migration,and angiogenesis.Local DIO enzymes fine-tune T3/T4 levels,with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion.Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk,whereas experimental models show inconsistent effects,reflecting regulation by hormone levels,receptor distribution,and tumor molecular features.Bibliometric analyses reveal a shift from epidemiological studies to molecular,immune,and metabolic mechanistic research,though clinical translation remains limited.This review synthesizes current knowledge on THs in PCa,highlighting mechanistic insights,evidence gaps,and future directions,aiming to inform early detection,stratification,and therapeutic strategies.
文摘Emerging biomarkers,such as tumor mutational burden and circulating tumor DNA(ctDNA),offer promising tools for identifying patients with prostate cancer who may benefit from immune checkpoint inhibitor therapy.This report describes an exceptional response to pembrolizumab in a patient with a microsatellite stability metastatic castration-resistant prostate cancer and ultrahigh tumor mutational burden.Additionally,this case further emphasizes the utility of ctDNA for monitoring molecular residual disease in patients whose disease burden is not adequately reflected by prostate-specific antigen levels and supports the use of ctDNA as a biomarker for personalized treat-ment monitoring and guiding treatment de-escalation.
文摘Prostate cancer is a significant global health issue with inflammation emerging as a critical driver of progression.The prostate tumor microenvironment(TME)is comprised of tumor cells,mesenchymal stem cells,immune cells,cancer-associated fibroblasts,adipocytes,and the extracellular matrix.All of these TME components interact via soluble factors,such as growth factors,cytokines,and chemokines.These interactions remodel the TME and drive inflammation and tumor progression.Prolonged inflammation leads to dysregulated activation and infiltration of immune cells in the TME.This process maintains an immunosuppressive environment and facilitates epithelial-to-mesenchymal transition,migration,and invasion.Chronic inflammation causes inflammatory mediators to enter the circulation over time,as evidenced by systemic biomarkers,such as the systemic immune-inflammation index,which links inflammation to disease severity.Interactions between the prostate gland and adipose tissues further exacerbate systemic inflammation.Inflammation in the prostate gland confers resistance to therapy,primes distant metastatic niches,and promotes metastatic spread,resulting in poor clinical outcomes.Therapeutic strategies,such as anti-inflammatory agents and immunotherapies,hold promise in mitigating disease burden.This review explored the immune landscape of systemic inflammation in prostate cancer,discussed the role of the immune landscape in resistance to therapy and metastasis,and offered insights into potential interventions for targeting inflammation to limit prostate cancer burden.
文摘The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.
文摘BACKGROUND The development of prostate cancer(PC)frequently intensifies negative emotional states,such as anxiety and depression,which compromise the effectiveness of radical surgery and reduce treatment adherence.In this study,we hypothesized that psychological resilience plays a crucial role in this process and explored its impact.AIM To investigate the association of resilience with anxiety and depression in patients with PC and to analyze the influencing factors.METHODS We selected 147 patients with PC who visited Qingdao Traditional Chinese Medicine Hospital from January 2022 to June 2024.The resilience scores of patients with PC were assessed using the Connor-Davidson Resilience Scale(CDRISC)from the tenacity,self-improvement,and optimism dimensions.Based on the total CD-RISC score,patients were categorized into groups A(total CD-RISC score>63 points,n=69)and B(total CD-RISC score≤63 points,n=78)for comparative analysis of anxiety[Hamilton Anxiety Rating Scale(HAMA)],depression[Hamilton Depression Rating Scale(HAMD)],sexual function[International Index of Erectile Function-5(IIEF-5)and Sexual Life Quality Questionnaire-Quality of Life(SLQQ-QOL)],and quality of life[the EORTC Core Quality of Life Question naire(QLQ-C30)].The association between CD-RISC and the above indicators was analyzed with Spearman correlation coefficients,and the influencing factors of resilience in patients with PC were identified with binary logistic regression.RESULTS Group A demonstrated statistically lower HAMA and HAMD scores and markedly higher scores of IIEF-5,SLQQQOL,and various QLQ-C30 aspects.Correlation analysis revealed that CD-RISC was significantly negatively correlated with HAMA and HAMD scores and significantly positively correlated with IIEF-5,SLQQ-QOL,and QLQ-C30 total scores.Binary logistic regression analysis revealed educational and per capita monthly household income levels as significant influencing factors of resilience in patients with PC.CONCLUSION Our results indicate a significant correlation of resilience with anxiety and depression in patients with PC.The milder the anxiety and depression emotions in patients,the higher their resilience.Further,assisting patients with PC to improve their educational and per capita monthly household income levels will help their resilience to some extent.
文摘Purpose:While the mental health impact of a prostate cancer diagnosis,including low-risk prostate cancer,is well-documented,the effect of pre-existing anxiety and/or depression on adherence to active surveillance protocols in low-risk prostate cancer patients remains unclear.This study assessed the association between prior anxiety and/or depression and active surveillance adherence in men with low-risk prostate cancer.Methods:We conducted a retrospective,multicenter study involving 426 men diagnosed with low-risk prostate cancer who were recommended active surveillance as the primary management strategy.Active surveillance adherence was defined by completion of both a prostate-specific antigen test and a prostate biopsy within 18 months of diagnosis.Premature treatment was identified as definitive treatment,either through radiation therapy or radical prostatectomy.Results:Men with a prior mental health diagnosis were significantly less likely to adhere to active surveillance than those without such a diagnosis(27.6%vs.49.5%,p=0.006).These individuals had lower adherence rates for prostate-specific testing(58.6%vs.73.4%)and biopsy(27.6%vs.50.0%)and were more likely to abandon active surveillance in favor of immediate treatment(39.7%vs.25.0%,p=0.005).No significant differences were observed between patients with both anxiety and depression versus those with a single diagnosis.Conclusions:Pre-existing anxiety and/or depression is associated with reduced active surveillance adherence and a greater likelihood of premature treatment in men with low-risk prostate cancer.These findings highlight the importance of addressing psychiatric factors in lowrisk prostate cancer management and suggest avenues for future research.
基金supported by Guangxi Natural Science Foundation(No.2023GXNSFDA026047)Guangxi Science and Technology Project(No.FANGKE ZY20221502)+1 种基金the National Natural Science Foundation of China(No.82160948)the Advanced Innovation Teams and Xinghu Scholars Program of Guangxi Medical University。
文摘Xiaoaiping(XAP)Injection demonstrates the anti-prostate cancer(PCa)effects,yet the underlying mechanism remains unclear.This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action.PCa cell proliferation was evaluated using a cell counting kit-8(CCK-8)assay.Cell apoptosis was assessed through Hoechst staining and Western blotting assays.Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells.To further validate potential key genes and important pathways,a series of assays were conducted,including acridine orange(AO)staining,transmission electron microscopy,and immunofluorescence assays.The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model.Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines.In C4-2 and prostate cancer cell line-3(PC3)cells,XAP induced cellular apoptosis,evidenced by reduced B-cell lymphoma 2(Bcl-2)levels and elevated Bcl-2-associated X(Bax)levels.Proteomic,immunofluorescence,and quantitative reverse transcription-polymerase chain reaction(q RT-PCR)investigations revealed a strong correlation between forkhead box O3a(FoxO3a)autophagic degradation and the anti-PCa action of XAP.XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5(Atg5)/autophagy-related protein 12(Atg12)and enhancing FoxO3a expression and nuclear translocation.Furthermore,XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue.These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation,potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
文摘Background:Transrectal(TR)and transperineal(TP)biopsies are commonly used methods for diagnosing prostate cancer.However,their comparative effectiveness in conjunction with machine learning(ML)techniques remains underexplored.This study aimed to evaluate the predictive accuracy of ML algorithms in detecting prostate cancer using data derived from TR and TP biopsies.Methods:The clinical records of patients who underwent prostate biopsy at King Saud University Medical City and King Faisal Specialist Hospital and Research Centerin Riyadh,Saudi Arabia,between 2018 and 2025 were analyzed.Data were used to train and testMLmodels,including eXtreme Gradient Boosting(XGBoost),Decision Tree,Random Forest,and Extra Trees.Results:The two datasets are comparable.The models demonstrated exceptional performance,achieving accuracies of up to 96.49%and 95.56%on TP and TR biopsy datasets,respectively.The area under the curve(AUC)values were also high,reaching 0.9988 for TP and 0.9903 for TR biopsy predictions.Conclusion:These findings highlight the potential of MLto enhance the diagnostic accuracy of prostate cancer detection irrespective of the biopsy method.However,TP biopsy data showed marginally higher accuracy,possibly because of the lower risk of contamination.While ML holds great promise for transforming prostate cancer care,further research is needed to address limitations.Collaboration between clinicians,data scientists,and researchers is crucial to ensure the clinical relevance and interpretability of ML models.
文摘Prostate cancer (PCa) is the second most common type of cancer among men worldwide and one of the leading causes of cancer-related deaths. According to data from the World Health Organization (WHO), this cancer causes hundreds of thousands of new cases and tens of thousands of male deaths globally each year. The incidence of PCa varies across different regions and populations, generally being higher in developed countries. This disparity may be attributed to lifestyle factors and the widespread availability of screening and diagnostic technologies. Prostate-specific membrane antigen (PSMA) is a membrane-bound enzyme predominantly expressed in prostate tissue and PCa cells, with lower expression in normal tissues. This high expression makes PSMA a critical target for the diagnosis and treatment of PCa, particularly in the field of molecular imaging and radiopharmaceutical therapy. Recently, various studies have emerged on radiopharmaceuticals developed based on PSMA ligands, which can be used to specifically identify and locate PCa cells. Research on the radiomics of these novel drugs has also been updated. This article will discuss the role and limitations of PSMA PET in the diagnosis and management of PCa treatment.
文摘As a practicing anatomic pathologist specialized in urologic pathology,a vast difference may be observed between what pathologists designate as neuroendocrine(or small cell)carcinoma of the prostate,and what clinicians or basic scientists define as such.
基金supported by Natural Science Foundation of Jilin Province(No.SKL202302002)Key Research and Development project of Jilin Provincial Science and Technology Department(No.20210204142YY)+2 种基金The Science and Technology Development Program of Jilin Province(No.2020122256JC)Beijing Kechuang Medical Development Foundation Fund of China(No.KC2023-JX-0186BQ079)Talent Reserve Program(TRP),the First Hospital of Jilin University(No.JDYY-TRP-2024007)。
文摘Prostate cancer(PCa)is characterized by high incidence and propensity for easy metastasis,presenting significant challenges in clinical diagnosis and treatment.Tumor microenvironment(TME)-responsive nanomaterials provide a promising prospect for imaging-guided precision therapy.Considering that tumor-derived alkaline phosphatase(ALP)is over-expressed in metastatic PCa,it makes a great chance to develop a theranostics system with ALP responsive in the TME.Herein,an ALP-responsive aggregationinduced emission luminogens(AIEgens)nanoprobe AMNF self-assembly was designed for enhancing the diagnosis and treatment of metastatic PCa.The nanoprobe exhibited self-aggregation in the presence of ALP resulted in aggregation-induced fluorescence,and enhanced accumulation and prolonged retention period at the tumor site.In terms of detection,the fluorescence(FL)/computed tomography(CT)/magnetic resonance(MR)multi-mode imaging effect of nanoprobe was significantly improved post-aggregation,enabling precise diagnosis through the amalgamation of multiple imaging modes.Enhanced CT/MR imaging can achieve assist preoperative tumor diagnosis,and enhanced FL imaging technology can achieve“intraoperative visual navigation”,showing its potential application value in clinical tumor detection and surgical guidance.In terms of treatment,AMNF showed strong absorption in the near infrared region after aggregation,which improved the photothermal treatment effect.Overall,our work developed an effective aggregation-enhanced theranostic strategy for ALP-related cancers.
基金supported in part by DOD Idea Development Award(HT9425-23-1-0295)NIH grants(R01 CA265897 and R21 CA280467)by the Department of Urology,University of Pittsburgh School of Medicine,Pittsburgh,PA,USA。
文摘Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most important target for prostate cancer treatment.Current USA Food and Drug Administration(FDA)-approved AR inhibitors target the ligand-binding domain(LBD)and have exhibited efficacy in prostate cancer patients,particularly when used in combination with androgen deprivation therapy.Unfortunately,patients treated with the currently approved AR-targeting agents develop resistance and relapse with castration-resistant prostate cancer(CRPC).The major mechanism leading to CRPC involves reactivation of AR signaling mainly through AR gene amplification,mutation,and/or splice variants.To effectively inhibit the reactivated AR signaling,new approaches to target AR are being actively explored.These new approaches include novel small molecule inhibitors targeting various domains of AR and agents that can degrade AR.The present review provides a summary of the existing FDA-approved AR antagonists and the current development of some of the AR targeting agents.
基金supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project number(PNURSP2025R104),Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘One in every eight men in the US is diagnosed with prostate cancer,making it the most common cancer in men.Gleason grading is one of the most essential diagnostic and prognostic factors for planning the treatment of prostate cancer patients.Traditionally,urological pathologists perform the grading by scoring the morphological pattern,known as the Gleason pattern,in histopathology images.However,thismanual grading is highly subjective,suffers intra-and inter-pathologist variability and lacks reproducibility.An automated grading system could be more efficient,with no subjectivity and higher accuracy and reproducibility.Automated methods presented previously failed to achieve sufficient accuracy,lacked reproducibility and depended on high-resolution images such as 40×.This paper proposes an automated Gleason grading method,ProGENET,to accurately predict the grade using low-resolution images such as 10×.This method first divides the patient’s histopathology whole slide image(WSI)into patches.Then,it detects artifacts and tissue-less regions and predicts the patch-wise grade using an ensemble network of CNN and transformer models.The proposed method adapted the International Society of Urological Pathology(ISUP)grading system and achieved 90.8%accuracy in classifying the patches into healthy and Gleason grades 1 through 5 using 10×WSI,outperforming the state-of-the-art accuracy by 27%.Finally,the patient’s grade was determined by combining the patch-wise results.The method was also demonstrated for 4−class grading and binary classification of prostate cancer,achieving 93.0%and 99.6%accuracy,respectively.The reproducibility was over 90%.Since the proposedmethod determined the grades with higher accuracy and reproducibility using low-resolution images,it is more reliable and effective than existing methods and can potentially improve subsequent therapy decisions.
基金supported financially by the National Nature Science Foundation of China(No.82373355,No.82172703,No.82303856,and No.82473505)the Discipline Leader Project of Shanghai Municipal Health Commission(No.2022XD013)the AoXiang Project of Shanghai Anti-Cancer Association(No.SACA-AX202302).
文摘The choice of biopsy method is critical in diagnosing prostate cancer(PCa).This retrospective cohort study compared systematic biopsy(SB)or cognitive fusion-targeted biopsy combined with SB(CB)in detecting PCa and clinically significant prostate cancer(csPCa).Data from 2572 men who underwent either SB or CB in Fudan University Shanghai Cancer Center(Shanghai,China)between January 2019 and December 2023 were analyzed.Propensity score matching(PSM)was used to balance baseline characteristics,and detection rates were compared before and after PSM.Subgroup analyses based on prostate-specific antigen(PSA)levels and Prostate Imaging-Reporting and Data System(PI-RADS)scores were performed.Primary and secondary outcomes were the detection rates of PCa and csPCa,respectively.Of 2572 men,1778 were included in the PSM analysis.Before PSM,CB had higher detection rates for both PCa(62.9%vs 52.4%,odds ratio[OR]:1.54,P<0.001)and csPCa(54.9%vs 43.3%,OR:1.60,P<0.001)compared to SB.After PSM,CB remained superior in detecting PCa(63.1%vs 47.9%,OR:1.86,P<0.001)and csPCa(55.0%vs 38.2%,OR:1.98,P<0.001).In patients with PSA 4–12 ng ml−1(>4 ng ml-1 and≤12 ng ml-1,which is also applicable to the following text),CB detected more PCa(59.8%vs 40.7%,OR:2.17,P<0.001)and csPCa(48.1%vs 27.7%,OR:2.42,P<0.001).CB also showed superior csPCa detection in those with PI-RADS 3 lesions(32.1%vs 18.0%,OR:2.15,P=0.038).Overall,CB significantly improves PCa and csPCa detection,especially in patients with PSA 4–12 ng ml−1 or PI-RADS 3 lesions.
基金supported by the National Key R&D Program of China(2022YFA1305700 to Li J)the“Dawn”Program of Shanghai Education Commission,China(21SG33 to Li J)The National Natural Science Foundation of China(82272793 to Gao X).
文摘Objective:Prostate cancer(PCa)exhibits significant genomic differences between Western and Asian populations.This study aimed to design a predictive model applicable across diverse populations while selecting a limited set of genes suitable for clinical implementation.Methods:We utilized an integrated dataset of 1360 whole-exome and whole-genome sequences from Chinese and Western PCa cohorts to develop and evaluate the model.External validation was conducted using an independent cohort of patients.A graph neural network architecture,termed the pathway-aware multi-layered hierarchical network-Western and Asian(P-NETwa),was developed and trained on combined genomic profiles from Chinese and Western cohorts.The model employed a multilayer perceptron(MLP)to identify key signature genes from multiomics data,enabling precise prediction of PCa metastasis.Results:The model achieved an accuracy of 0.87 and an F1-score of 0.85 on Western population datasets.The application of integrated Chinese and Western population data improved the accuracy to 0.88,achieving an F1-score of 0.75.The analysis identified 18 signature genes implicated in PCa progression,including established markers(AR and TP53)and novel candidates(MUC16,MUC4,and ASB12).For clinical adoption,the model was optimized for commercially available gene panels while maintaining high classification accuracy.Additionally,a user-friendly web interface was developed to facilitate real-time prediction of primary versus metastatic status using the pre-trained P-NETwa-MLP model.Conclusion:The P-NETwa-MLP model integrates a query system that allows for efficient retrieval of prediction outcomes and associated genomic signatures via sample ID,enhancing its potential for seamless integration into clinical workflows.
