Explainable and visualizable machine learning models to predict biochemical recurrence of prostate cancer.

PURPOSE: Machine learning (ML) models presented an excellent performance in the prognosis prediction. However, the black box characteristic of ML models limited the clinical applications. Here, we aimed to establish explainable and visualizable ML models to predict biochemical recurrence (BCR) of prostate cancer (PCa). MATERIALS AND METHODS: A total of 647 PCa patients were retrospectively evaluated. Clinical parameters were identified using LASSO regression. Then, cohort was split into training and validation datasets with a ratio of 0.75:0.25 and BCR-related features were included in Cox regression and five ML algorithm to construct BCR prediction models. The clinical utility of each model was evaluated by concordance index (C-index) values and decision curve analyses (DCA). Besides, Shapley Additive Explanation (SHAP) values were used to explain the features in the models. RESULTS: We identified 11 BCR-related features using LASSO regression, then establishing five ML-based models, including random survival forest (RSF), survival support vector machine (SSVM), survival Tree (sTree), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and a Cox regression model, C-index were 0.846 (95%CI 0.796-0.894), 0.774 (95%CI 0.712-0.834), 0.757 (95%CI 0.694-0.818), 0.820 (95%CI 0.765-0.869), 0.793 (95%CI 0.735-0.852), and 0.807 (95%CI 0.753-0.858), respectively. The DCA showed that RSF model had significant advantages over all models. In interpretability of ML models, the SHAP value demonstrated the tangible contribution of each feature in RSF model. CONCLUSIONS: Our score system provide reference for the identification for BCR, and the crafting of a framework for making therapeutic decisions for PCa on a personalized basis.

Clinical risk prediction model and external validation of positive surgical margin in laparoscopic radical prostatectomy based on MRI lesion location.

OBJECTIVE: To clarify the composition of lesions in different magnetic resonance imaging (MRI) partitions of positive surgical margins (PSM) after laparoscopic radical prostatectomy, explore the influence of lesion location on PSM, and construct a clinical prediction model to predict the risk of PSM. MATERIALS AND METHODS: This retrospective cohort study included 309 patients who underwent laparoscopic radical prostatectomy from 2018 to 2021 in our center was performed. 129 patients who met the same criteria from January to September 2022 were external validation cohorts. RESULTS: The incidence of PSM in transition zone (TZ) lesions was higher than that in peripheral zone (PZ) lesions. The incidence of PSM in the middle PZ was lower than that in other regions. Prostate specific antigen (PSA), clinical T-stage, the number of positive cores, international society of urological pathology (ISUP) grade (biopsy), MRI lesion location, extracapsular extension, seminal vesicle invasion (SVI), pseudo-capsule invasion (PCI), long diameter of lesions, lesion volume, lesion volume ratio, PSA density were related to PSM. MRI lesion location and PCI were independent risk factors for PSM. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a clinical prediction model for PSM, including five variables: the number of positive cores, SVI, MRI lesion location, long diameter of lesions, and PSA. CONCLUSION: The positive rate of surgical margin in middle PZ was significantly lower than that in other regions, and MRI lesion location was an independent risk factor for PSM.

Bright, photostable and long-circulating NIR-II nanoparticles for whole-process monitoring and evaluation of renal transplantation.

Kidney transplantation is the gold standard for the treatment of end-stage renal diseases (ESRDs). However, the scarcity of donor kidneys has caused more and more ESRD patients to be stuck on the waiting list for transplant surgery. Improving the survival rate for renal grafts is an alternative solution to the shortage of donor kidneys. Therefore, real-time monitoring of the surgical process is crucial to the success of kidney transplantation, but efficient methods and techniques are lacking. Herein, a fluorescence technology based on bright, photostable and long-circulating aggregation-induced emission (AIE) active NIR-II nano-contrast agent DIPT-ICF nanoparticles for the whole-process monitoring and evaluation of renal transplantation has been reported. In the aggregated state, DIPT-ICF exhibits superior photophysical properties compared with the commercial dyes IR-26 and IR-1061. Besides, the long-circulating characteristic of the AIE nano-contrast agent helps to achieve renal angiography in kidney retrieval surgery, donor kidney quality evaluation, diagnosing vascular and ureteral complications, and assessment of renal graft reperfusion beyond renovascular reconstruction, which considerably outperforms the clinically approved indocyanine green (ICG).

Comparison of percutaneous nephrolithotomy and flexible ureterorenoscopy in the treatment of single upper ureteral calculi measuring 1 to 2 centimeters: a retrospective study.

PURPOSE: To compare the efficacy and safety of micropercutaneous nephrolithotomy (MPCNL) and flexible ureteroscopy (FURS) in the treatment of single upper ureteral calculi measuring 1 to 2 centimeters. METHODS: This study is a retrospective analysis that combines a review of medical records with an outcomes management database. A total of 163 patients who underwent MPCNL and 137 patients who had FURS were identified between January 2017 and December 2021. Demographic data, operation time, hospitalization time, stone-free rate, and complication rate were collected and analyzed. RESULTS: Preoperative general data of sex, age, BMI, serum creatinine, time of stone existence, stone hardness, stone diameter, preoperative hydronephrosis, and preoperative infection of the MPCNL group have no statistically significant difference with that of the FURS group. All MPCNL or FURS operations in both groups were successfully completed without any instances of reoperation or conversion to another surgical procedure. Patients who underwent MPCNL had a considerably reduced operation time (49.6 vs. 72.4 min; P<0.001), but a higher duration of hospitalization (9.1 vs. 3.9 days; P<0.001) compared to those who underwent FURS. The stone-free rate in the MPCNL group was superior to that of the FURS group, with a percentage of 90.8% compared to 71.5% (P<0.001). There was no statistically significant disparity in the rate of complications between the two groups (13.5% vs. 15.3%; P = 0.741). CONCLUSION: Both MPCNL and FURS are viable and secure surgical choices for individuals with solitary upper ureteral calculi measuring 1 to 2 cm. The FURS procedure resulted in a shorter duration of hospitalization compared to MPCNL. However, it had a comparatively lower rate of successfully removing the stones and required a longer duration for the operation.There were no substantial disparities observed in the complication rate between the two groups.FURS is the preferable option for treating uncomplicated upper ureteral calculi, whereas MPCNL is the preferable option for treating complicated upper ureteral calculi.Prior to making treatment options, it is crucial to take into account the expertise of surgeons, the quality of the equipment, and the preferences of the patient. TRIAL REGISTRATION: No.

Recent strategies for evoking immunogenic Pyroptosis in antitumor immunotherapy.

Pyroptosis is a specific type of programmed cell death (PCD) characterized by distinct morphological changes, including cell swelling, membrane blebbing, DNA fragmentation, and eventual cell lysis. Pyroptosis is closely associated with human-related diseases, such as inflammation and malignancies. Since the initial observation of pyroptosis in Shigella flexneri-infected macrophages more than 20 years ago, various pyroptosis-inducing agents, including ions, small molecules, and biological nanomaterials, have been developed for tumor treatment. Given that pyroptosis can activate the body's robust immune response against tumor and promote the formation of the body's long-term immune memory in tumor treatment, its status as a type of immunogenic cell death is self-evident. Therefore, pyroptosis should be used as a powerful anti-tumor strategy. However, there still is a lack of a comprehensive summary of the most recent advances in pyroptosis-based cancer therapy. Therefore, it is vital to fill this gap and inspire future drug design to better induce tumor cells to undergo pyroptosis to achieve advanced anti-tumor effects. In this review, we summarize in detail the most recent advances in triggering tumor cell immunogenic pyroptosis for adequate tumor clearance based on various treatment modalities, and highlight material design and therapeutic advantages. Besides, we also provide an outlook on the prospects of this emerging field in the next development.

Risk Factors and Short-Term Prognosis of Lymphocele After Kidney Transplant.

OBJECTIVES: Lymphocele is a frequent complication after kidney transplant and needs attention. This study was undertaken to analyze perioperative risk factors and short-term outcomes associated with lymphocele after kidney transplant. MATERIALS AND METHODS: Our single-center study retrospectively analyzed 264 recipients of kidney allografts from January 2018 to October 2021. Patients were classified into 2 groups according to the occurrence of lymphocele. Perioperative clinical data and follow-up indicators were compared between groups. RESULTS: The incidence of lymphocele after kidney transplant was 19.7%. Univariate analysis showed that percentage of male patients, hypothermic machine perfusion proportion, and postoperative hemoglobin and albumin were lower and flow velocity of renal artery was higher in the lymphocele group compared with the control group. Multivariate logistic regression revealed that postoperative hemoglobin <95 g/L (odds ratio = 2.01; 95% confidence interval, 1.01-4.05; P = .03) was an independent risk factor and hypothermic machine perfusion (odds ratio = 0.27; 95% confidence interval, 0.08-0.96; P = .04) was a protective factor for the determination of lymphocele. Comparisons of related complications indicated that drainage tube and urinary catheter removal times were longer and urinary tract infection and moderate to severe anemia proportions were higher in the lymphocele group. Follow-up data showed that postoperative 1-month serum creatinine was higher and 1-month estimated glomerular filtration rate was lower in lymphocele group compared with the control group, but no significant differences were shown at 12 months. CONCLUSIONS: Postoperative hemoglobin may be a risk factor and hypothermic machine perfusion may be a protective factor for lymphocele after kidney transplant. Lymphocele only temporarily affects short-term kidney function, especially during hospitalization.

A novel clinically significant prostate cancer prediction system with multiparametric MRI and PSA: P.Z.A. score.

PURPOSE: This study aims to establish and validate a new diagnosis model called P.Z.A. score for clinically significant prostate cancer (csPCa). METHODS: The demographic and clinical characteristics of 956 patients were recorded. Age, prostate-specific antigen (PSA), free/total PSA (f/tPSA), PSA density (PSAD), peripheral zone volume ratio (PZ-ratio), and adjusted PSAD of PZ (aPSADPZ) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The nomogram was established, and discrimination abilities of the new nomogram were verified with a calibration curve and area under the ROC curve (AUC). The clinical benefits of P.Z.A. score were evaluated by decision curve analysis and clinical impact curves. External validation of the model using the validation set was also performed. RESULTS: The AUCs of aPSADPZ, age, PSA, f/tPSA, PSAD and PZ-ratio were 0.824, 0.672, 0.684, 0.715, 0.792 and 0.717, respectively. The optimal threshold of P.Z.A. score was 0.41. The nomogram displayed excellent net benefit and better overall calibration for predicting the occurrence of csPCa. In addition, the number of patients with csPCa predicted by P.Z.A. score was in good agreement with the actual number of patients with csPCa in the high-risk threshold. The validation set provided better validation of the model. CONCLUSION: P.Z.A. score (including PIRADS(P), aPSADPZ(Z) and age(A)) can increase the detection rate of csPCa, which may decrease the risk of misdiagnosis and reduce the number of unnecessary biopsies. P.Z.A. score contains data that is easy to obtain and is worthy of clinical replication.

Artificial intelligence-aided detection for prostate cancer with multimodal routine health check-up data: an Asian multi-center study.

BACKGROUND: The early detection of high-grade prostate cancer (HGPCa) is of great importance. However, the current detection strategies result in a high rate of negative biopsies and high medical costs. In this study, the authors aimed to establish an Asian Prostate Cancer Artificial intelligence (APCA) score with no extra cost other than routine health check-ups to predict the risk of HGPCa. PATIENTS AND METHODS: A total of 7476 patients with routine health check-up data who underwent prostate biopsies from January 2008 to December 2021 in eight referral centres in Asia were screened. After data pre-processing and cleaning, 5037 patients and 117 features were analyzed. Seven AI-based algorithms were tested for feature selection and seven AI-based algorithms were tested for classification, with the best combination applied for model construction. The APAC score was established in the CH cohort and validated in a multi-centre cohort and in each validation cohort to evaluate its generalizability in different Asian regions. The performance of the models was evaluated using area under the receiver operating characteristic curve (ROC), calibration plot, and decision curve analyses. RESULTS: Eighteen features were involved in the APCA score predicting HGPCa, with some of these markers not previously used in prostate cancer diagnosis. The area under the curve (AUC) was 0.76 (95% CI:0.74-0.78) in the multi-centre validation cohort and the increment of AUC (APCA vs. PSA) was 0.16 (95% CI:0.13-0.20). The calibration plots yielded a high degree of coherence and the decision curve analysis yielded a higher net clinical benefit. Applying the APCA score could reduce unnecessary biopsies by 20.2% and 38.4%, at the risk of missing 5.0% and 10.0% of HGPCa cases in the multi-centre validation cohort, respectively. CONCLUSIONS: The APCA score based on routine health check-ups could reduce unnecessary prostate biopsies without additional examinations in Asian populations. Further prospective population-based studies are warranted to confirm these results.

Dual-Pronged Attack: pH-Driven Membrane-Anchored NIR Dual-Type Nano-Photosensitizer Excites Immunogenic Pyroptosis and Sequester Immune Checkpoint for Enhanced Prostate Cancer Photo-Immunotherapy.

Prostate cancer (PCa) is a frustrating immunogenic "cold" tumor and generally receives unsatisfied immunotherapy outcomes in the clinic. Pyroptosis is an excellent immunogenic cell death form that can effectively activate the antitumor immune response, promote cytotoxic T-lymphocyte infiltration, and convert tumors from "cold" to "hot." However, the in vivo application of pyroptosis drugs is seriously limited, and the upregulation of tumor PD-L1 caused by photo-immunotherapy further promotes immune escape. Herein, a new nano-photosensitizer (YBS-BMS NPs-RKC) with pH-response integrating immunogenic pyroptosis induction and immune checkpoint blockade is developed. The pH-responsive polymer equipped with the cell membrane anchoring peptide RKC is used as the carrier and further encapsulated with the near-infrared-activated semiconductor polymer photosensitizer YBS and a PD-1/PD-L1 complex small molecule inhibitor BMS-202. The pH-driven membrane-anchoring and pyroptosis activation of YBS-BMS NPs-RKC is clearly demonstrated. In vitro and in vivo studies have shown that this dual-pronged therapy stimulates a powerful antitumor immune response to suppress primary tumor progression and evokes long-term immune memory to inhibit tumor relapse and metastasis. This work provides an effective self-synergistic platform for PCa immunotherapy and a new idea for developing more biocompatible photo-controlled pyroptosis inducers.

Analysis of the efficacy of a single subumbilical stoma for bilateral cutaneous ureterostomy after radical cystectomy.

BACKGROUND: Radical cystectomy and urinary diversion are the standard surgical treatments for patients with muscle-invasive or high-risk, or recurrent non-muscle-invasive bladder cancer. Although this approach significantly prolongs patient survival, it can lead to postoperative complications. This study aims to compare the efficacy and complications of bilateral cutaneous ureterostomy with a single subumbilical stoma to those of cutaneous ureterostomy with two stomas and an ileal conduit as a means of urinary diversion after radical cystectomy. The findings of this study will provide valuable information for healthcare providers in selecting the appropriate urinary diversion method for their patients. METHODS: The clinical data for 108 patients who received bilateral cutaneous ureterostomy with a single subumbilical stoma (ureterostomy with a single stoma group), cutaneous ureterostomy with two stomas (ureterostomy with two stomas group), or an ileal conduit (ileal conduit group) after radical cystectomy were retrospectively analysed. The operative time, pathological stage, survival status, perioperative complication rate, rate of successful first extubation, rehospitalization rate at 6 months after surgery,ostomy-related medical costs,and postoperative quality of life were compared between the three groups of patients. RESULTS: A significant difference in the operative time was found between the three groups (P = 0.001). No significant differences in pathological stage, survival status, perioperative complication rate, rehospitalization rate at 6 months after surgery, or bladder cancer index (BCI) score were identified among the three groups. The difference in the successful first extubation rate between the three groups of patients was significant (P = 0.001). Significant differences in ostomy-related medical costs were observed among the three groups of patients (P = 0.006). CONCLUSION: A single subumbilical stoma for bilateral cutaneous ureterostomy after radical cystectomy may result in shorter surgery time, increased success rates for initial catheter removal, and lower medical expenses. However, to confirm these findings, further prospective randomized clinical trials are necessary.

Artificial intelligence for the diagnosis of clinically significant prostate cancer based on multimodal data: a multicenter study.

BACKGROUND: The introduction of multiparameter MRI and novel biomarkers has greatly improved the prediction of clinically significant prostate cancer (csPCa). However, decision-making regarding prostate biopsy and prebiopsy examinations is still difficult. We aimed to establish a quick and economic tool to improve the detection of csPCa based on routinely performed clinical examinations through an automated machine learning platform (AutoML). METHODS: This study included a multicenter retrospective cohort and two prospective cohorts with 4747 cases from 9 hospitals across China. The multimodal data, including demographics, clinical characteristics, laboratory tests, and ultrasound reports, of consecutive participants were retrieved using extract-transform-load tools. AutoML was applied to explore potential data processing patterns and the most suitable algorithm to build the Prostate Cancer Artificial Intelligence Diagnostic System (PCAIDS). The diagnostic performance was determined by the receiver operating characteristic curve (ROC) for discriminating csPCa from insignificant prostate cancer (PCa) and benign disease. The clinical utility was evaluated by decision curve analysis (DCA) and waterfall plots. RESULTS: The random forest algorithm was applied in the feature selection, and the AutoML algorithm was applied for model establishment. The area under the curve (AUC) value in identifying csPCa was 0.853 in the training cohort, 0.820 in the validation cohort, 0.807 in the Changhai prospective cohort, and 0.850 in the Zhongda prospective cohort. DCA showed that the PCAIDS was superior to PSA or fPSA/tPSA for diagnosing csPCa with a higher net benefit for all threshold probabilities in all cohorts. Setting a fixed sensitivity of 95%, a total of 32.2%, 17.6%, and 26.3% of unnecessary biopsies could be avoided with less than 5% of csPCa missed in the validation cohort, Changhai and Zhongda prospective cohorts, respectively. CONCLUSIONS: The PCAIDS was an effective tool to inform decision-making regarding the need for prostate biopsy and prebiopsy examinations such as mpMRI. Further prospective and international studies are warranted to validate the findings of this study. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100048428. Registered on 06 July 2021.

Extracapsular extension of transitional zone prostate cancer miss-detected by multiparametric magnetic resonance imaging.

OBJECTIVES: To demonstrate the importance of extracapsular extension (ECE) of transitional zone (TZ) prostate cancer (PCa), examine the causes of its missed detection by Mp-MRI, and develop a new predictive model by integrating multi-level clinical variables. MATERIALS AND METHODS: This retrospective study included 304 patients who underwent laparoscopic radical prostatectomy after 12 + X needle transperineal transrectal ultrasound (TRUS)-MRI-guided targeted prostate biopsy from 2018 to 2021 in our center was performed. RESULTS: In this study, the incidence rates of ECE were similar in patients with MRI lesions in the peripheral zone (PZ) and TZ (P = 0.66). However, the missed detection rate was higher in patients with TZ lesions than in those with PZ lesions (P < 0.05). These missed detections result in a higher positive surgical margin rate (P < 0.05). In patients with TZ lesions, detected MP-MRI ECE may have grey areas: the longest diameters of the MRI lesions were 16.5-23.5 mm; MRI lesion volumes were 0.63-2.51 ml; MRI lesion volume ratios were 2.75-8.86%; PSA were 13.85-23.05 ng/ml. LASSO regression was used to construct a clinical prediction model for predicting the risk of ECE in TZ lesions from the perspective of MRI and clinical features, including four variables: the longest diameter of MRI lesions, TZ pseudocapsule invasion, ISUP grading of biopsy pathology, and number of positive biopsy needles. CONCLUSIONS: Patients with MRI lesions in the TZ have the same incidence of ECE as those with lesions in the PZ, but a higher missed detection rate.

Cr(OH)3nanosheets@ZIF67 electrocatalysts prepared by electrodeposition method for efficient oxygen evolution reaction.

In this paper, a Cr(OH)3NSs@ZIF67 (NSs = nanosheets) electrocatalyst is prepared on foam Ni via a simple and rapid electrochemical deposition method. Excellent electrocatalytic activity of Cr(OH)3NSs@ZIF67 is demonstrated. It can use the overpotential of 281 mV and 390 mV respectively to drive 10 mA cm-2and 50 mA cm-2. It is observed that the Cr(OH)3NSs@ZIF67 electrode has the highest initial current density at 1.57 V compared with the other two monomer electrodes and shows excellent stability at the end of 60 000 s. It has the largest electrochemical activity specific surface and lowest charge-transfer resistance, and M-O bonds (M = Co, Cr) and shifting of binding energy peaks at the interface lead to more active sites and more efficient electron transfer for oxygen evolution reaction. This work highlights the construction of highly efficient composite electrocatalysts composted of low-dimensional non-precious transition metal compounds and metalorganic frameworks, promoting the development of low-cost non-noble metal composites in energy chemistry.

New model of PIRADS and adjusted prostatespecific antigen density of peripheral zone improves the detection rate of initial prostate biopsy: a diagnostic study.

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.

Development and validation of a nomogram for predicting the overall survival of prostate cancer patients: a large population-based cohort study.

Background: Prostate cancer (PC) is the second most common malignant tumor, and its survival is of great concern. However, the assessment of survival risk in current studies is limited. This study is to develop and validate a nomogram for the prediction of survival in PC patients using data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: A total of 153,796 PC patients were included in this cohort study. Patients were divided into a training set (n=107,657) and a testing set (n=46,139). The 3-, 5- and 10-year survival of the PC patients were regarded as the outcomes. Predictors based on the demographic and pathological data for survival were identified by multivariate Cox regression analysis to develop the predictive nomogram. Internal and subgroup validations were performed to assess the predictive performance of the nomogram. The C-index, time-dependent receiver operating characteristic (ROC) curves, and corresponding areas under the ROC curves (AUCs) were used to estimate the predictive performance of the nomogram. Results: Age at diagnosis, race, marital status, tumor node metastasis (TNM) stage, prostate specific antigen (PSA) status, Gleason score, and pathological stage were identified as significantly associated with the survival of PC patients (P<0.05). The C-index of the nomogram indicated a moderate predictive ability [training set: C-index =0.782, 95% confidence interval (CI): 0.779-0.785; testing set: C-index =0.782, 95% CI: 0.777-0.787]. The AUCs of this nomogram for the 3-, 5-, and 10-year survival were 0.757 (95% CI: 0.756-0.758), 0.741 (95% CI: 0.740-0.742), and 0.716 (95% CI: 0.715-0.717), respectively. The results of subgroup validation showed that all the AUCs for the nomogram at 3, 5, and 10 years were more than 0.70, regardless of marital status and race. Conclusions: We developed a nomogram with the moderate predictive ability for the long-term survival (3-, 5-, and 10-year survival) of patients with PC.

Glycolytic potential enhanced by blockade of pyruvate influx into mitochondria sensitizes prostate cancer to detection and radiotherapy.

OBJECTIVE: This study aimed to evaluate the effects of mitochondrial pyruvate carrier (MPC) blockade on the sensitivity of detection and radiotherapy of prostate cancer (PCa). METHODS: We investigated glycolysis reprogramming and MPC changes in patients with PCa by using metabolic profiling, RNA-Seq, and tissue microarrays. Transient blockade of pyruvate influx into mitochondria was observed in cellular studies to detect its different effects on prostate carcinoma cells and benign prostate cells. Xenograft mouse models were injected with an MPC inhibitor to evaluate the sensitivity of 18F-fluorodeoxyglucose positron emission tomography with computed tomography and radiotherapy of PCa. Furthermore, the molecular mechanism of this different effect of transient blockage towards benign prostate cells and prostate cancer cells was studied in vitro. RESULTS: MPC was elevated in PCa tissue compared with benign prostate tissue, but decreased during cancer progression. The transient blockade increased PCa cell proliferation while decreasing benign prostate cell proliferation, thus increasing the sensitivity of PCa cells to 18F-PET/CT (SUVavg, P = 0.016; SUVmax, P = 0.03) and radiotherapy (P < 0.01). This differential effect of MPC on PCa and benign prostate cells was dependent on regulation by a VDAC1-MPC-mitochondrial homeostasis-glycolysis pathway. CONCLUSIONS: Blockade of pyruvate influx into mitochondria increased glycolysis levels in PCa but not in non-carcinoma prostate tissue. This transient blockage sensitized PCa to both detection and radiotherapy, thus indicating that glycolytic potential is a novel mechanism underlying PCa progression. The change in the mitochondrial pyruvate influx caused by transient MPC blockade provides a critical target for PCa diagnosis and treatment.

New Diagnostic Model for Clinically Significant Prostate Cancer in Biopsy-Naïve Men With PIRADS 3.

Purpose: The aim of this study was to explore a new model of clinical decision-making to predict the occurrence of clinically significant prostate cancer (csPCa). Patients and Methods: The demographic and clinical characteristics of 152 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), adjusted PSAD of peripheral zone (aPSADPZ), and peripheral zone volume ratio (PZ ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. Results: The AUCs of PSA, PSAD, aPSADPZ, and PZ ratio were 0.521, 0.645, 0.745, and 0.717 for prostate cancer (PCa) diagnosis, while the corresponding values were 0.590, 0.678, 0.780, and 0.731 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of csPCa. The new model significantly improved the diagnostic accuracy of csPCa (0.865 vs. 0.741, p = 0.0284) compared with the base model. In addition, the new model was better than the base model for predicting csPCa in the low or medium probability while the number of patients with csPCa predicted by the new model was in good agreement with the actual number of patients with csPCa in the high-risk threshold. Conclusions: This study demonstrates that aPSADPZ has a higher predictive accuracy for csPCa diagnosis than the conventional indicators. Including aPSADPZ, PZ ratio, and age can improve csPCa diagnosis and avoid unnecessary biopsies.

Comparison of MRI/US Fusion Targeted Biopsy and Systematic Biopsy in Biopsy-Naïve Prostate Patients with Elevated Prostate-Specific Antigen: A Diagnostic Study.

Purpose: This study aimed to compare the detection rate of prostate cancer (PCa) between targeted biopsy and systematic biopsy. Patients and Methods: A total of 671 patients who underwent both targeted biopsy and systematic biopsy were included in this study. The stratified analysis was conducted based on Prostate Imaging Reporting and Data System (PIRADS) scores, region of interest load (ROI-load). Results: There was no statistical difference in the detection rate of PCa patients between systematic biopsy and targeted biopsy (44.41% vs 45.6%, P>0.05), while the detection rate of targeted biopsy in clinically significant PCa (csPCa) patients was slightly higher than that of systematic biopsy (40.83% vs 38.15%, P=0.033). Stratified analysis indicated that targeted biopsy was more advantageous in csPCa patients with PIRADS score ≥ 4 and ROI-load > 5%. The comparison of diagnostic sensitivity of systematic biopsy and targeted biopsy demonstrated that targeted biopsy was more sensitive than systematic biopsy to diagnose PCa (Z=2.110, P=0.035) at ROI-load ≤ 5%. In addition, ROI-load may be a better targeted biopsy indicator than ROI diameter for the diagnosis of PCa (Z=2.168, P=0.030). Conclusion: MRI/US fusion targeted biopsy may be more suitable for PCa detection than systematic biopsy in patients with low ROI-load.

A correlative study of iron metabolism based on q-Dixon MRI in benign prostatic hyperplasia and prostate cancer.

Clinical staging, Gleason score, and prostate-specific antigen (PSA) have been accepted as factors for evaluating the prognosis of prostate cancer (PCa). With the in-depth study of iron metabolism and the development of multiparametric magnetic resonance imaging technology, we used q-Dixon magnetic resonance imaging (MRI) to measure the iron content of the PCa patients' lesions, and used enzyme-linked immunosorbent assay (ELISA) to measure the iron metabolism indicators in the patients' serum samples, combined with the patients' postoperative clinical data for analysis. We found that the serum indexes were correlated with the T2 star values, International Society of Urological Pathology (ISUP) grade, and pathological classification in PCa patients (all P < 0.001) but not in benign prostatic hyperplasia (BPH) patients (all P > 0.05). The utilization of q-Dixon-based MRI and serum indexes allows the noninvasive measurement of iron content in prostate lesions and the assessment of differential iron metabolism between PCa and BPH, which may be helpful for evaluating the prognosis of PCa.

FOXD1-AS1 promotes malignant behaviours of prostate cancer cells via the miR-3167/YWHAZ axis.

Herein, the effect of long noncoding RNA forkhead box D1 antisense RNA 1 (FOXD1-AS1) on malignant phenotypes of prostate cancer (PCa) cells was investigated. FOXD1-AS1 presented high expression in PCa cells according to the results of RT-qPCR. As shown by cell counting kit-8 assays, colony formation assays, wound-healing assays, Transwell assays and flow cytometry analyses, silenced FOXD1-AS1 suppressed PCa cell viability, proliferation, migration and invasion and enhanced cell apoptosis. Additionally, FOXD1-AS1 was primarily localised in cytoplasm of PCa cells. RNA immunoprecipitation assays and luciferase reporter assays revealed that FOXD1-AS1 interacted with miR-3167 in PCa cells. MiR-3167 functioned as an anti-oncogene in PCa and miR-3167 overexpression suppressed cell proliferation while promoted cell apoptosis. Moreover, the downstream target of miR-3167 is mRNA YWHAZ. FOXD1-AS1 elevated the expression of YWHAZ by binding with miR-3167. The suppressive effect of miR-3167 on YWHAZ expression was reversed by FOXD1-AS1 overexpression. Furthermore, overexpressed YWHAZ reversed the suppressive effect of FOXD1-AS1 deficiency on malignant behaviours of PCa cells. Overall, FOXD1-AS1 facilitates malignant phenotypes of PCa cells by up-regulating YWHAZ via miR-3167. The study first reveals the molecular mechanism of FOXD1-AS1 in PCa, suggesting that FOXD1-AS1 and its downstream molecules might be prognostic biomarkers before medical treatment.