Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts

BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.

Transurethral prostate surgery in prostate cancer patients: A population-based comparative analysis of complication and mortality rates

Objective:Prostate cancer(PCa)patients might experience lower urinary tract symptoms as those diagnosed with benign prostatic hyperplasia(BPH).Some of them might be treated for their lower urinary tract symptoms instead of PCa.We aimed to test the effect of PCa versus BPH on surgical outcomes after transurethral prostate surgery,namely complication and mortality rates.Methods:Within the American College of Surgeons National Surgical Quality Improvement Program database(2011-2016),we identified patients who underwent transurethral resection of the prostate,photoselective vaporization,or laser enucleation.Patients were stratified according to postoperative diagnosis(PCa vs.BPH).Univariable and multivariable logistic regression models evaluated the predictors of perioperative morbidity and mortality.A formal test of interaction between diagnosis and surgical technique used was performed.Results:Overall,34542 patients were included.Of all,2008(5.8%)had a diagnosis of PCa.The multivariable logistic regression model failed to show statistically significant higher rates of postoperative complications in PCa patients(odds ratio:0.9,95%confidence interval:0.7-1.1;p=0.252).Moreover,similar rates of perioperative mortality(p=0.255),major acute cardiovascular events(p=0.581),transfusions(p=0.933),and length of stay of more than or equal to 30 days(p=0.174)were found.Additionally,all tests failed to show an interaction between post-operative diagnosis and surgical technique used.Conclusion:Patients diagnosed with PCa do not experience higher perioperative morbidity or mortality after transurethral prostate surgery when compared to their BPH counterparts.Moreover,the diagnosis seems to not influence surgical technique outcomes.

Aminated Cyclopropylmethylphosphonates as Potent Prostate Cancer Inhibitors

Inspired by the anti-pancreatic promising results of our novel aminated cyclopropylmethylphosphonate compounds, an in vitro anti-prostate cancer activity exploration of these compounds was carried out on human prostate cancer cell line PC-3, and showed potent inhibiting activity at low micromolar concentrations (with an IC50 of approximately 45 μM).

Treatment-induced neuroendocrine prostate cancer and de novo neuroendocrine prostate cancer:Identification,prognosis and survival,genetic and epigenetic factors

Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer.NEPC may arise de novo or develop following androgen deprivation therapy(ADT).NEPC that arise following ADT has the nomenclature“treatmentemerging/induced NEPC(t-NEPC)”.t-NEPC would be anticipated in castration resistant prostate cancer(CRPC)and metastatic PCa.t-NEPC is characterized by low or absent androgen receptor(AR)expression,independence of AR signaling,and gain of neuroendocrine phenotype.t-NEPC is an aggressive metastatic tumor,develops from PCa in response to drug induced ADT,and shows very short response to conventional therapy.t-NEPC occurs in 10%-17%of patients with CRPC.De novo NEPC is rare and is accounting for less than 2%of all PCa.The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated.Sphingosine kinase 1 plays a significant role in t-NEPC development.Although neuroendocrine markers:Synaptophysin,chromogranin A,and insulinoma associated protein 1(INSM1)are expressed in t-NEPC,they are non-specific for diagnosis,prognosis,and follow-up of therapy.t-NEPC shows enriched genomic alteration in tumor protein P53(TP53)and retinoblastoma 1(RB1).There are evidences suggest that t-NEPC might develop through epigenetic evolution.There are genomic,epigenetic,and transcriptional alterations that are reported to be involved in development of t-NEPC.Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC.PCa is resistant to immunotherapy,and at present there are running trials to approach immunotherapy for PCa,CRPC,and t-NEPC.

Application of prostate resectoscope in the treatment of massive rectal bleeding after transrectal prostate puncture

BACKGROUND Ultrasound-guided prostate biopsy is a reliable diagnostic procedure for prostate cancer diagnosis with minimal procedure-related trauma.However,complications,such as massive rectal bleeding may occur after the puncture.We hypothesized that using a transrectal resectoscope could help treat massive rectal bleeding after transrectal prostate punctures.AIM To identify a simple and effective treatment for massive rectal bleeding after transrectal prostate punctures.METHODS Patients requiring treatment for massive rectal bleeding after transrectal prostate punctures were included.A SIMAI resectoscope was inserted through the anus.Direct electrocoagulation was performed for superficial bleeding points.Part of the rectal mucosa or surface muscle layer was removed to expose deep bleeding points,followed by electrocoagulation.An electric cutting ring was used to compress and stop the bleeding for jet-like points before electrocoagulation.The fluid color in the drainage tube was monitored postoperatively for continuous bleeding.RESULTS Eight patients were included from 2012 to 2022.None of the patients with massive rectal bleeding after the transrectal prostate punctures improved with conventional conservative and blood transfusion treatments.Two patients had an inferior artery embolism,and digital subtraction angiography was ineffective.All patients received emergency transanal prostate resection,which immediately stopped the bleeding.Four days after the procedure,the patients had recovered and were discharged.CONCLUSION Using a transanal prostate resection instrument is a simple,safe,and effective method for treating massive rectal bleeding after transrectal prostate punctures.

Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of PCa.Methods:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University.The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa.The expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques.To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa.The Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical significance.Results:ASPA was identified as a novel inhibitor of PCa progression.The expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,migration,and invasion,respectively.The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models.Mechanistically,ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets,JNK1/2 and C-Jun,in both PCa cells and mouse models,in an enzyme-independent manner.Importantly,the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models.Moreover,we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples,suggesting a potential regulatory role of ASPA in modulating LYN signaling.Conclusions:Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.

Icariin plus curcumol enhances autophagy through the mTOR pathway and promotes cathepsin B-mediated pyroptosis of prostate cancer cells

Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation.Autophagy expression was analyzed using monodansylcadaverine staining.Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR pathway.Cellular damage was examined using the lactate dehydrogenase assay.Moreover,cathepsin B and NLRP3 were detected by co-immunoprecipitation.Results:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy.The levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol.These changes were reversed upon overexpression of mTOR.Furthermore,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol group.Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.Conclusions:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B.These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.

Effects of heat stress and long photoperiod on the prostate of rats

Objective:To examine light and heat effects on the morphological,histological,and micrometric structure of the prostate of rats.Methods:Thirty adult male rats were divided into three groups.The control group was kept under 20℃-22℃ and an artificial 12 h/12 h day/night cycle;the temperature group was under normal light and at(42±1)℃ heat for 4 to 5 h daily,and the light group was exposed to 8 h/16 h day/night cycle with 20℃-22℃.Rats were weighed five times(at the beginning of the study and every seven days).Five milliliters(mL)of their peripheral blood were taken.The tissue staining was performed using the hematoxylin-eosin(H&E)stain and periodic acid-Schiff(PAS).In the following,tissue and cellular reactions to the PAS were examined.Results:Folds were located entirely on the surface of the anterior lobe and periphery of the other lobes.The secretory units in the anterior lobe were more than the lateral lobe.A strong reaction of the secretory cells to the PAS was observed.Testosterone serum levels of the light group also significantly increased compared to the control group(P<0.05).The most histometric changes of the lobes were established in the lateral lobes.Heat stress resulted in a significant decrease in testosterone levels and transformed prostate tissue.The epithelium and parenchyma to scaffold ratio in the temperature group decreased.Conclusions:Maximum and minimum changes in the ventral lobe happened under the ascent of temperature and light,respectively.The ventral lobe in the study of prostatic hyperplasia should be more considered.

Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer:A meta-analysis and systematic review

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases.Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model.Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: −0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24).Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

Genetic variant in a BaP-activated super-enhancer increases prostate cancer risk by promoting AhR-mediated FAM227A expression

Genetic variants in super-enhancers(SEs)are increasingly implicated as a disease risk-driving mechanism.Previous studies have reported an associations between benzo[a]pyrene(BaP)exposure and some malignant tumor risk.Currently,it is unclear whether BaP is involved in the effect of genetic variants in SEs on prostate cancer risk,nor the associated intrinsic molecular mechanisms.In the current study,by using logistic regression analysis,we found that rs5750581T>C in 22q-SE was significantly associated with prostate cancer risk(odds ratio=1.26,P=7.61×10^(-5)).We also have found that the rs6001092T>G,in a high linkage disequilibrium with rs5750581T>C(r^(2)=0.98),is located in a regulatory aryl hydrocarbon receptor(AhR)motif and may interact with the FAM227A promoter in further bioinformatics analysis.We then performed a series of functional and BaP acute exposure experiments to assess biological function of the genetic variant and the target gene.Biologically,the rs6001092-G allele strengthened the transcription factor binding affinity to AhR,thereby upregulating FAM227A,especially upon exposure to BaP,which induced the malignant phenotypes of prostate cancer.The current study highlights that AhR acts as an environmental sensor of BaP and is involved in the SE-mediated prostate cancer risk,which may provide new insights into the etiology of prostate cancer associated with the inherited SE variants under environmental carcinogen stressors.

Contribution of Bone Scintigraphy in the Metastatic Extension Assessment of Prostate Cancer: A Study of 288 Cases in the Nuclear Medicine Department of Idrissa Pouye General Hospital, Dakar

Introduction: Prostate cancer is the most frequently diagnosed male malignancy and the fifth leading cause of cancer death in men worldwide. Since the advent of screening methods such as Prostate Specific Antigen (PSA) assay, digital rectal examination (DRE) and prostate biopsy, its incidence has increased significantly. The aim of our study was to analyse aspects of bone scintigraphy (BS) as part of the metastatic extension assessment of prostate cancer in Senegal. Patients and Methods: This was a retrospective descriptive and analytical study, running from January 1er 2022 to August 31 2023. Patients with histologically confirmed prostate cancer were included. Whole-body scans (WBS) were performed using a dual-head SPECT gamma camera (Mediso Nucline TM Spirit DH-V type), 3 hours after intravenous injection of 8 MBq/kg (555 to 740 MBq) of 99mTc-HMDP. Results: A total of 288 patients with a mean age of 68.37 ± 7.79 years were included. The median total PSA level was 97.6 ng/ml, with 144 patients having a level greater than or equal to 20 ng/ml. All patients had adenocarcinoma, and the Gleason score was available in 202 (70.13%) patients, 75.75% of whom had a score greater than or equal to 7. BS was contributory in 70.48% of cases, with 30.90% positive and 39.58% negative. The result was inconclusive in 85 patients (29.51%). The mean PSA for patients with a positive scan was 190.2 ng/ml and 40.6 ng/ml for those with a negative scan. Multiple metastatic lesions predominated (87.35% of cases). Metastatic lesions occurred preferentially in the axial skeleton, with a proportion of 68% versus 32% in the appendicular skeleton. Classification of bone metastases according to the SOLOWAY score revealed grade I (62.07%), grade II (35.63%) and grade IV (2.30%). Conclusion: In Senegal, prostate cancer is generally diagnosed in men of advanced age. The presence of bone metastases is frequent in its evolution, transforming a curable localized disease into a generalized disease with a compromised prognosis. Bone scintigraphy remains an essential part of the initial work-up and evaluation of response to treatment.

MAPK9 as a therapeutic target:unveiling ferroptosis in localized prostate cancer progression

Background:Ferroptosis,a lipid peroxidation-mediated programmed cell death,is closely linked to tumor development,including prostate cancer(PCa).Despite established connections between ferroptosis and PCa,a comprehensive investigation is essential for understanding its impact on patient prognosis.Methods:A risk model incorporating four ferroptosis-related genes was developed and validated.Elevated risk scores correlated with an increased likelihood of biochemical recurrence(BCR),diminished immune infiltration,and adverse clinicopathological characteristics.To corroborate these results,we performed validation analyses utilizing datasets from both the Cancer Genome Atlas Cohort(TCGA)and the Gene Expression Synthesis Cohort(GEO).Moreover,we conducted further investigations into the pivotal gene identified in our model to explore its impact on tumor characteristics through cell proliferation and invasion assays,as well as animal studies conducted in vivo.Additionally,we conducted further experiments involving ferroptosis-related analysis to validate its association with ferroptosis.Results:The risk model demonstrated exceptional predictive capabilities for prognosis and therapeutic outcomes in PCa patients.Mitogen-activated protein kinase 9(MAPK9)emerged as a crucial gene within the model.In vivo and in vitro experiments explored MAPK9’s role in ferroptosis and its influence on tumor migration and proliferation.Conclusion:The findings provide a novel perspective for advancing ferroptosis exploration in PCa,bridging basic research and clinical applications.

Epidemiological and Histopathological Profile of Prostate Cancer: A Retrospective Study in the Pathology Department of the University Clinics of Kinshasa

Background: Prostate cancer, the most common male cancer, represents a real public health problem in terms of its frequency and severity in different countries around the world. It disproportionately affects people of African descent wherever they live in the world [1]. To the best of our knowledge, its extent and particularities in the African environment are not well known. Objective: To determine the epidemiological and histopathological profile of prostate cancer in the CUK anatomopathology department. Methodology: This is a retrospective study conducted at the University Clinics of Kinshasa Anapathology Department from January 1, 2015 to December 31, 2022, a period of 8 years. Word processing and tables were entered using the Hp brand computer, with Microsoft Office WORD 2016 software. Data analysis was performed with SPSS version 22.0 software. Results were presented in tables and figures. Results: Prostate was diagnosed in 132 cases, i.e. 1.58% of all CUK laboratory analyses and 8% of cancers diagnosed. The age group most affected was 66-75 years, i.e. 59% of all subjects. Adenocarcinoma was the most frequent histological type, and biopsy dominated in 111 cases (84.1%). Conclusion: Prostate cancer is a real public health problem. Worldwide, and in the Democratic Republic of Congo, it is the most frequently diagnosed cancer in men, and the leading cause of cancer-related death in men. In the DRC, because of the delay in consulting our patients and the weakness of systematic screening, patients are seen at an advanced stage of the disease. Treatment is multidisciplinary, involving surgery, radiotherapy and chemotherapy (including targeted therapies). Patient awareness and screening campaigns will help to considerably reduce the delay in diagnosis and the morbidity and mortality associated with prostate cancer.

CircTHSD4 promotes the malignancy and docetaxel (DTX) resistance in prostate cancer by regulating miR-203/HMGA2 axis

Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and docetaxel(DTX)resistance of PCa.Methods:circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real time reverse transcription quantitative polymerase chain reaction(RT-qPCR).In addition,a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa cells.In addition,we performed a Western blot(WB)assay to detect high mobility.group A2 protein(HMGA2)levels.Besides,functional associations of two molecules were investigated through dual luciferase reporter assay.Cell Counting Kit(CCK)-8,colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells,whereas flow cytometry was performed to determine cell apoptosis.Furthermore,a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa cells.Results:According to RT-qPCR results,circTHSD4 was up-regulated within PCa tissues and cells,which predicted the dismal prognostic outcome of PCa cases.circTHSD4 silencing within PCa cells markedly suppressed cell growth,migration,and colony fomation.circTHSD4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft model.Further,circTHSD4 silencing enhanced docetaxel(DTX)sensitivity in PCa cells.Furthermore,we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR 203.Conclusion:Together,our findings suggest that cirCTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR 203/HMGA2 axis.

Attention Guided Multi Scale Feature Fusion Network for Automatic Prostate Segmentation

The precise and automatic segmentation of prostate magnetic resonance imaging(MRI)images is vital for assisting doctors in diagnosing prostate diseases.In recent years,many advanced methods have been applied to prostate segmentation,but due to the variability caused by prostate diseases,automatic segmentation of the prostate presents significant challenges.In this paper,we propose an attention-guided multi-scale feature fusion network(AGMSF-Net)to segment prostate MRI images.We propose an attention mechanism for extracting multi-scale features,and introduce a 3D transformer module to enhance global feature representation by adding it during the transition phase from encoder to decoder.In the decoder stage,a feature fusion module is proposed to obtain global context information.We evaluate our model on MRI images of the prostate acquired from a local hospital.The relative volume difference(RVD)and dice similarity coefficient(DSC)between the results of automatic prostate segmentation and ground truth were 1.21%and 93.68%,respectively.To quantitatively evaluate prostate volume on MRI,which is of significant clinical significance,we propose a unique AGMSF-Net.The essential performance evaluation and validation experiments have demonstrated the effectiveness of our method in automatic prostate segmentation.

Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related RNA splicing

The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the associations.We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify riskassociated circRNAs by using the MiOncoCirc database.We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4662 prostate cancer patients and 3114 healthy controls,and identified circHIBADH rs11973492 T>C as a significant risk-associated variant(odds ratio=1.20,95%confidence interval:1.08-1.34,P=7.06×10^(-4))in a dominant genetic model,which altered the secondary structure of the corresponding RNA chain.In the in silico analysis,we found that circHIBADH sponged and silenced 21 RNA-binding proteins(RBPs)enriched in the RNA splicing pathway,among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house(four tissue samples)and publicly available single-cell transcriptomes.Additionally,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting carcinogenesis.In conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.

Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

What benefit can be obtained from magnetic resonance imaging diagnosis with artificial intelligence in prostate cancer compared with clinical assessments?

The present study aimed to explore the potential of artificial intelligence(AI)methodology based on magnetic resonance(MR)images to aid in the management of prostate cancer(PCa).To this end,we reviewed and summarized the studies comparing the diagnostic and predictive performance for PCa between AI and common clinical assessment methods based on MR images and/or clinical characteristics,thereby investigating whether AI methods are generally superior to common clinical assessment methods for the diagnosis and prediction fields of PCa.First,we found that,in the included studies of the present study,AI methods were generally equal to or better than the clinical assessment methods for the risk assessment of PCa,such as risk stratification of prostate lesions and the prediction of therapeutic outcomes or PCa progression.In particular,for the diagnosis of clinically significant PCa,the AI methods achieved a higher summary receiver operator characteristic curve(SROC-AUC)than that of the clinical assessment methods(0.87 vs.0.82).For the prediction of adverse pathology,the AI methods also achieved a higher SROC-AUC than that of the clinical assessment methods(0.86 vs.0.75).Second,as revealed by the radiomics quality score(RQS),the studies included in the present study presented a relatively high total average RQS of 15.2(11.0–20.0).Further,the scores of the individual RQS elements implied that the AI models in these studies were constructed with relatively perfect and standard radiomics processes,but the exact generalizability and clinical practicality of the AI models should be further validated using higher levels of evidence,such as prospective studies and open-testing datasets.

Unraveling the biological link between diabetes mellitus and prostate cancer:Insights and implications

This article is a comprehensive study based on research on the connection between diabetes mellitus(DM)and prostate cancer(PCa).It investigates the potential role of DM as an independent risk factor for PCa,delving into the biological links,including insulin resistance and hormonal changes.The paper critically analyzes previous studies that have shown varying results and introduces mendelian randomization as a method for establishing causality.It emphasizes the importance of early DM screening and lifestyle modifications in preventing PCa,and proposes future research directions for further understanding the DM-PCa relationship.

Unlocking the potential-vitamin D in prostate cancer prevention

Prostate cancer poses a significant health challenge globally,demanding proactive prevention strategies.This editorial explores the emerging role of vitamin D in prostate cancer prevention.While traditionally associated with bone health,vitamin D is increasingly recognized for its broader impact on immune function,cellular signaling,and cancer prevention.Epidemiological studies suggest an intriguing link between vitamin D deficiency and elevated prostate cancer risk,particularly in regions with limited sunlight exposure.Mechanistically,vitamin D regulates cellular processes,inhibiting unchecked cancer cell growth and bols-tering immune surveillance.Personalized prevention strategies,considering individual factors,are deemed essential for harnessing the full potential of vitamin D.To unlock this potential,the future calls for robust research,public awareness campaigns,dietary improvements,and vigilant medical guidance.Collaborative efforts are poised to pave the way toward a future where vitamin D stands as a sentinel in prostate cancer prevention,ushering in hope and improved health for men worldwide.