Prostate Volume Growth Rate Changes over Time:Results from Men 18 to 92 Years Old in a Longitudinal Community-based Study

Previous investigations have shown that changes in total prostate volume（TPV） are highly variable among aging men,and a considerable proportion of aging men have a stable or decreasing prostate size.Although there is an abundance of literature describing prostatic enlargement in association with benign prostatic hyperplasia,less is known about the appropriate age cut-off points for TPV growth rate.In this community-based cohort study,TPV was examined once a year in men who had consecutive health checkup,during a follow-up of 4 years.A total of 5058 men（age 18–92 years old） were included.We applied multiple regression analyses to estimate the correlation between TPV growth rate and age.Overall,3232（63.9%） men had prostate growth,and 1826（36.1%） had a stable or decreased TPV during the study period.The TPV growth rate was correlated negatively with baseline TPV（r= –0.32,P〈0.001）.Among 2620 men with baseline TPV 〈15 cm^3,the TPV growth rate increased with age（β=0.98,95% CI：0.77%–1.18%） only up to 53 years old.Among 2188 men with baseline TPV of 15–33.6 cm3,the TPV growth rate increased with age（β=0.84,95% CI,0.66%–1.01%） only up to 61 years old after adjusting for factors of hypertension,obesity,baseline TPV,diabetes mellitus and dyslipidemia.In this longitudinal study,the TPV growth rate increased negatively with baseline TPV,only extending to a certain age and not beyond.Further research is needed to identify the mechanism underlying such differences in prostate growth.

A nomogram based on age, prostate-specific antigen level, prostate volume and digital rectal examination for predicting risk of prostate cancer

Nomograms for predicting the risk of prostate cancer developed using other populations may introduce sizable bias when applied to a Chinese cohort. In the present study, we sought to develop a nomogram for predicting the probability of a positive initial prostate biopsy in a Chinese population. A total of 535 Chinese men who underwent a prostatic biopsy for the detection of prostate cancer in the past decade with complete biopsy data were included. Stepwise logistic regression was used to determine the independent predictors of a positive initial biopsy. Age, prostate-specific antigen （PSA）, prostate volume （PV）, digital rectal examination （DRE） status, % free PSA and transrectal ultrasound （TRUS） findings were included in the analysis. A nomogram model was developed that was based on these independent predictors to calculate the probability of a positive initial prostate biopsy. A receiver-operating characteristic curve was used to assess the accuracy of using the nomogram and PSA levels alone for predicting positive prostate biopsy. The rate for positive initial prostate biopsy was 41.7% （223/535）. The independent variables used to predict a positive initial prostate biopsy were age, PSA, PV and DRE status. The areas under the receiver-operating characteristic curve for a positive initial prostate biopsy for PSA alone and the nomogram were 79.7% and 84.8%, respectively. Our results indicate that the risk of a positive initial prostate biopsy can be predicted to a satisfactory level in a Chinese population using our nomogram. The nomogram can be used to identify and counsel patients who should consider a prostate biopsy, ultimately enhancing accuracy in diagnosing prostate cancer.

Prostate volume as an independent predictor of prostate ：ancer in men with PSA of 10-50 ng ml-1

Prostate volume （PV） has been shown to be associated with prostate cancer （PCa） detection rates in men with a prostate-specific antigen （PSA） in the ＇grey zone＇ （2.0-10.0 ng ml-1）. However, the PSA ＇grey zone＇ in Asian men should be higher because the incidence of PCa in Asian men is relatively low. Therefore, we evaluated the association between PV and PCa detection rates in men with PSAs measuring 10-50 ng ml-1, Men who underwent a 13-core prostatic biopsy with PV documentation participated in the study. A multivariate stepwise regression was used to evaluate whether the PV at time of prostate biopsy could predict the risk of PCa. The rates of PCa among men in different PSA ranges, stratified by PV medians （〈60 and ≥60 ml）, were calculated. There were 261 men included in the final analysis. PV was the strongest predictor of PCa risk （odds ratio, 0.02; P〈0.001） compared to other variables. The PCa rates in men with PVs measuring 〈60 and ≥ 60 ml in the 10-19.9 ng ml-1 PSA group were 40.6% and 15.1%, respectively, while the rates for men with PSAs measuring 20-50 ng ml- 1 were 65.1% and 26.8%. PV is an independent predictor of PCa in men with PSA measuring 10-50 ng ml-1. In clinical practice, particularly for those countries with lower incidences of PCa, PV should be considered when counselling patients with PSAs measuring 10-50 ng ml-1 regarding their PCa risks.

The influence of prostate volume on cancer detection in the Chinese population

In western populations, prostate volume （PV） has been proven to be one of the strongest predictors of detecting prostate cancer （PCa） in biopsies. We performed this study in a biopsy cohort, to evaluate associations among the prostate volume, prostate-specific antigen （PSA） and PCa detection in the Chinese population. Between the years, 2007-13, 1486 men underwent prostate biopsy at Huashan Hospital, Fudan University, Shanghai, China. The study population was divided into two groups for analysis according to total PSA （tPSA） range （4 ng m1-1 〈tPSA 〈20 ng m1-1 and tPSA 〉20 ng ml-1）. PV, age, tPSA, digital rectal examination （DRE） and transrectal ultrasound （TRUS） results were also included in the analysis. Although the positive biopsy rates decreased in both tPSA range groups, the downtrend was more pronounced in the 4 ng ml-2 〈tPSA 〈20 ng m1-1 group; therefore, we focused on 853 men in this group with increasing PV. In multivariate logistic regression analysis, only DRE was found to be associated with PCa in four PV groups （P 〈 0.05） and tPSA did not show a good predictive ability when PV exceeded 50 ml （P 〉 0.05）. Further, it may suggest that with increasing PV, the cancer detection rate decreased in men with different tPSA, DRE and TRUS nodule statuses （all P values for trends were 〈0.001）. Our study indicates that in tPSA ranging from 4 to 20 ng ml-1, the use of PV ranges of 0-35 ml, 35-50 ml and 〉50 ml might be taken into consideration for the biopsy decision-making in the Chinese population.

Serum prostate-specific antigen as a predictor of prostate volume and lower urinary tract symptoms in acommunity-based cohort： a large-scale Korean screening study

The aim of this study is to assess the ability of serum prostate-specific antigen （PSA） to predict prostate volume （PV） and lower urinary tract symptoms （LUTS） represented by the international prostate symptom score （IPSS）. From January 2001 to December 2011, data were collected from men who first enrolled in the Korean Prostate Health Council Screening Program. Patients with a serum PSA level of 10 ng ml^-1 or age 〈40 years were excluded. Accordingly, a total of 34 857 men were included in our study, and serum PSA, PV and the IPSS were estimated in all patients. Linear and age-adjusted multivariate logistic analyses were used to assess the potential association between PSA and PV or IPSS. The predictive value of PSA for estimating PV and IPSS was assessed based on the receiver operating characteristics-derived area under the curve （AUC）. The mean PV was 29.9 ml, mean PSA level was 1.49 ng ml^-1 and mean IPSS was 15.4. A significant relationship was shown between PSA and PV, and the IPSS and PSA were also significantly correlated after adjusting by age. The AUCs of PSA for predicting PV ~20 ml, 〉25 ml and 〉35 ml were 0.722, 0.728 and 0.779, respectively. The AUCs of PSA for predicting IPSS 〉 7, 〉 13 and 〉 19 were 0. 548, 0.536 and 0. 537, respectively. Serum PSA was a strong predictor of PV in a community-based cohort in a large-scale screening study. Although PSA was also significantly correlated with IPSS, predictive values of PSA for IPSS above the cutoff levels were not excellent. Further investigations are required to elucidate the exact interactions between PSA and LUTS and between PSA and PV in prospective controlled studies. Such studies may suggest how PSA can be used to clinically predict PV and the IPSS.

A novel equation and nomogram including body weight for estimating prostate volumes in men with biopsy-proven benign prostatic hyperplasia

Anthropometric measurements, e.g., body weight （BW）, body mass index （BMI）, as well as serum prostate-specific antigen （PSA） and percent-free PSA （%fPSA） have been shown to have positive correlations with total prostate volume （TPV）. We developed an equation and nomogram for estimating TPV, incorporating these predictors in men with benign prostatic hyperplasia （BPH）. A total of 1852 men, including 1113 at Tokyo Medical and Dental University （TMDU） Hospital as a training set and 739 at Cancer Institute Hospital （CIH） as a validation set, with PSA levels of up to 20 ng m1-1, who underwent extended prostate biopsy and were proved to have BPH, were enrolled in this study. We developed an equation for continuously coded TPV and a logistic regression-based nomogram for estimating a TPV grater than 40 mh Predictive accuracy and performance characteristics were assessed using an area under the receiver operating characteristics curve （AUC） and calibration plots. The final linear regression model indicated age, PSA, %fPSA and BW as independent predictors of continuously coded TPV. For predictions in the training set, the multiple correlation coefficient was increased from 0.38 for PSA alone to 0.60 in the final model. We developed a novel nomogram incorporating age, PSA, %fPSA and BW for estimating TPV greater than 40 mh External validation confirmed its predictive accuracy, with AUC value of 0.764. Calibration plots showed good agreement between predicted probability and observed proportion. In conclusion, TPV can be easily estimated using these four independent predictors.

Correlation of PSA Density to Prostate Cancer Based on Prostate Volume by 3.0 T MRI

Purpose: Prostate specific antigen levels can be normalized by the prostate volume to give a prostate specific antigen density (PSAd). Magnetic resonance imaging (MRI) can more accurately determine prostate zonal anatomy and prostate volumes compared to transrectal ultrasound, and hence may lead to more accurate PSAd measurements. Methods: Imaging and pathology of men undergoing prostate MRI from April 2007 to May 2009 were reviewed in this retrospective study. 73 patients were included for analysis, of which 45 had prostate cancer and 28 did not have cancer. Total, transitional zone, and peripheral zone values were determined by ultrasound prolate ellipse, MRI prolate ellipse, and MRI segmentation methods. Results: The study population showed an average PSA of 6.3 ng/mL, with the control mean PSA (8.8 ng/mL) being greater than the cancer group (5.3 ng/mL). Transrectal ultrasound underestimated the prostate volume (mean 27.7 mL versus MRI volume of 38.3 mL, p ≤ 0.001). No difference was seen between cancer and control populations using PSAd. PSAd correctly categorized low (Gleason < 7) and high-grade cancers (Gleason ≥ 7) in patients with malignancy. Conclusion: Transrectal ultrasound underestimates prostate volumes and hence is inaccurate in calculating PSAd. MRI more accurately depicts PSAd, however PSAd is unable to differentiate between patients with cancer and benign disease such as BPH or prostatitis.

The Effect of Prostate Volume on Robotic-assisted Radical Prostatectomy

Objective:To investigate the effect of prostate volume on robot-assisted radical prostatectomy.Methods:Clinical data of 75 patients underwent RARP in the Affiliated Hospital of Qingdao University were retrospectively analyzed.The patients were divided into 3 groups according to size of prostate.A total of 35 cases with prostate volume less than 30ml were recorded as group 1,27 cases with volume of 30 to 50 ml were recorded as group 2,and 13 cases with volume greater than 50ml were recorded as group 3.Age,BMI,preoperative PSA,operation time,intraoperative bleeding volume,postoperative drainage volume,indwelling time of catheter,indwelling time of drainage tube,total hospitalization time,pathological stage,surgical margin,urine control and biochemical recurrence were observed.Results:All operations were performed under Da Vinci robot assistance,and no patient was transferred to open surgery.There was no significant difference in age,preoperative PSA,BMI,operation time,intraoperative bleeding volume,postoperative drainage volume,indwelling time of catheter,total hospitalization time,pathological stage,rate of positive surgical margin and recovery of urinary continence between the groups.Indwelling time of drainage tube was longer in group with larger prostate,6.4(±4.5)days in group 1,6.3(±2.9)days in group 2 and 7.1(±2.5)days in group 3.Gleason score was lower in group with larger prostate,with statistical difference.Conclusion:Prostate volume had no significant effect on urinary control,rate of positive surgical margin and recurrence after RARP.Gleason score of pathological tissue was lower and indwelling time of drainage tube was longer in patients with larger prostate after RARP.Operation time and intraoperative bleeding volume of large prostate patients underwent RARP need to be further studied.RARP has certain advantages for patients with large prostate.

Correlation between dose-volume parameters and rectal bleeding after 12 fractions of carbon ion radiotherapy for prostate cancer

BACKGROUND Carbon ion radiotherapy(CIRT)is currently used to treat prostate cancer.Rectal bleeding is a major cause of toxicity even with CIRT.However,to date,a correlation between the dose and volume parameters of the 12 fractions of CIRT for prostate cancer and rectal bleeding has not been shown.Similarly,the clinical risk factors for rectal bleeding were absent after 12 fractions of CIRT.AIM To identify the risk factors for rectal bleeding in 12 fractions of CIRT for prostate cancer.METHODS Among 259 patients who received 51.6 Gy[relative biological effectiveness(RBE)],in 12 fractions of CIRT,15 had grade 1(5.8%)and nine had grade 2 rectal bleeding(3.5%).The dose-volume parameters included the volume(cc)of the rectum irradiated with at least x Gy(RBE)(Vx)and the minimum dose in the most irradiated x cc normal rectal volume(Dx).RESULTS The mean values of D6cc,D2cc,V10 Gy(RBE),V20 Gy(RBE),V30 Gy(RBE),and V40 Gy(RBE)were significantly higher in the patients with rectal bleeding than in those without.The cutoff values were D6cc=34.34 Gy(RBE),D2cc=46.46 Gy(RBE),V10 Gy(RBE)=9.85 cc,V20 Gy(RBE)=7.00 cc,V30 Gy(RBE)=6.91 cc,and V40 Gy(RBE)=4.26 cc.The D2cc,V10 Gy(RBE),and V20 Gy(RBE)cutoff values were significant predictors of grade 2 rectal bleeding.CONCLUSION The above dose-volume parameters may serve as guidelines for preventing rectal bleeding after 12 fractions of CIRT for prostate cancer.

Free PSA performs better than total PSA in predicting prostate volume in Chinese men with PSA levels of 2.5–9.9 ng ml−1

This study investigated whether free prostate-specific antigen(fPSA)performs better than total PSA(tPSA)in predicting prostate volume(PV)in Chinese men with different PSA levels.A total of 5463 men with PSA levels of<10 ng ml^(−1) and without prostate cancer diagnosis were included in this study.Patients were classified into four groups:PSA<2.5 ng ml^(−1),2.5–3.9 ng ml^(−1),4.0–9.9 ng ml^(−1),and 2.5–9.9 ng ml^(−1).Pearson/Spearman's correlation coefficient(r)and receiver operating characteristic(ROC)curves were used to evaluate the ability of tPSA and fPSA to predict PV.The correlation coefficient between tPSA and PV in the PSA<2.5 ng ml^(−1) cohort(r=0.422;P<0.001)was markedly higher than those of the cohorts with PSA levels of 2.5–3.9 ng ml^(−1),4.0–9.9 ng ml^(−1),and 2.5–9.9 ng ml^(−1)(r=0.114,0.167,and 0.264,respectively;all P≤0.001),while fPSA levels did not differ significantly among different PSA groups.Area under ROC curve(AUC)analyses revealed that the performance of fPSA in predicting PV≥40 ml(AUC:0.694,0.714,and 0.727)was better than that of tPSA(AUC=0.545,0.561,and 0.611)in men with PSA levels of 2.5–3.9 ng ml^(−1),4.0–9.9 ng ml^(−1),and 2.5–9.9 ng ml^(−1),respectively,but not at PSA levels of<2.5 ng ml^(−1)(AUC:0.713 vs 0.720).These findings suggest that the relationship between tPSA and PV may vary with PSA level and that fPSA is more powerful at predicting PV only in the"gray zone"(PSA levels of 2.5–9.9 ng ml^(−1)),but its performance was similar to that of tPSA at PSA levels of<2.5 ng ml^(−1).

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.

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.

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.

Double-face urethroplasty in patients with obliterative bulbar strictures post-transurethral resection of the prostate mid-term outcomes in high-volume referral center

Objective Incidences of post-transurethral resection of the prostate(post-TURP)strictures are between 2.2%and 9.8%.Stricture commonly occurs within the first 6 months.Our objective was to assess the outcomes of patients with obliterative strictures post-TURP that underwent a double-face urethroplasty.Methods This is a single-center prospective study of 17 patients with obliterative proximal bulbar stricture post-TURP who underwent double-face graft urethroplasty by two surgeons between January 2014 and January 2020.We defined post-TURP obliterative strictures as those patients who presented with complete or almost complete obstruction of the urethral lumen and who have had a history of acute urine retention.We have excluded patients with bladder neck contracture.Primary outcome was treatment success,defined as the no need for further treatments.Secondary outcome was post-urethroplasty continent rate.Results Seventeen patients were included in the study with median age of 66(interquartile range 40-77)years;median time of follow-up was 24(interquartile range 12-84)months;median stricture length was 4(interquartile range 2-6)cm.Of the 17 patients,15(88.2%)were successful.All patients were continent after urethroplasty.Conclusion With mid-term follow-up,treatment of obliterative proximal bulbar strictures with double-face buccal mucosa graft is a safe and effective procedure.Obliterative proximal bulbar strictures merit double-face urethroplasty with high-rate success and functional outcomes.

Analysis of risk factors leading to anxiety and depression in patients with prostate cancer after castration and the construction of a risk prediction model

BACKGROUND Cancer patients often suffer from severe stress reactions psychologically,such as anxiety and depression.Prostate cancer(PC)is one of the common cancer types,with most patients diagnosed at advanced stages that cannot be treated by radical surgery and which are accompanied by complications such as bodily pain and bone metastasis.Therefore,attention should be given to the mental health status of PC patients as well as physical adverse events in the course of clinical treatment.AIM To analyze the risk factors leading to anxiety and depression in PC patients after castration and build a risk prediction model.METHODS A retrospective analysis was performed on the data of 120 PC cases treated in Xi'an People's Hospital between January 2019 and January 2022.The patient cohort was divided into a training group(n=84)and a validation group(n=36)at a ratio of 7:3.The patients’anxiety symptoms and depression levels were assessed 2 wk after surgery with the Self-Rating Anxiety Scale(SAS)and the Selfrating Depression Scale(SDS),respectively.Logistic regression was used to analyze the risk factors affecting negative mood,and a risk prediction model was constructed.RESULTS In the training group,35 patients and 37 patients had an SAS score and an SDS score greater than or equal to 50,respectively.Based on the scores,we further subclassified patients into two groups:a bad mood group(n=35)and an emotional stability group(n=49).Multivariate logistic regression analysis showed that marital status,castration scheme,and postoperative Visual Analogue Scale(VAS)score were independent risk factors affecting a patient's bad mood(P<0.05).In the training and validation groups,patients with adverse emotions exhibited significantly higher risk scores than emotionally stable patients(P<0.0001).The area under the curve(AUC)of the risk prediction model for predicting bad mood in the training group was 0.743,the specificity was 70.96%,and the sensitivity was 66.03%,while in the validation group,the AUC,specificity,and sensitivity were 0.755,66.67%,and 76.19%,respectively.The Hosmer-Lemeshow test showed aχ^(2) of 4.2856,a P value of 0.830,and a C-index of 0.773(0.692-0.854).The calibration curve revealed that the predicted curve was basically consistent with the actual curve,and the calibration curve showed that the prediction model had good discrimination and accuracy.Decision curve analysis showed that the model had a high net profit.CONCLUSION In PC patients,marital status,castration scheme,and postoperative pain(VAS)score are important factors affecting postoperative anxiety and depression.The logistic regression model can be used to successfully predict the risk of adverse psychological emotions.

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.

Inflammatory response in gastrointestinal cancers:Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications

Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis.Unfortunately,due to the lack of effective therapeutic targets,the prognosis of patients with GICs is still unsatisfactory.Interestingly,it is found that six transmembrane epithelial antigens of the prostate(STEAPs),a group of metal reductases,are significantly associated with the progression of malignancies,playing a crucial role in systemic metabolic homeostasis and inflammatory responses.The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress,responding to inflammatory reactions.Under the imbalance status of abnormal oxidative stress,STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process.This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms,with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.

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.

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.

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.