American journal of clinical and experimental urology最新文献

Background: Studies have established a strong link between erectile dysfunction (ED) and genetic factors. However, the genetic protective genes associated with ED have yet to be identified. In this study, we used Mendelian randomization (MR) analysis to investigate potential genetic protective genes related to ED.

Methods: We used ED-associated GWAS data and whole blood expression quantitative trait loci (eQTLs) data from the Finnish database, which included 1,154 cases and 94,024 controls, for our analysis, resulting in a total of 95,178 individuals for Mendelian randomization (MR) analysis. To further identify potential causative genes and explore their functional roles and relationship to phenotype, we conducted PPI and single-cell analysis using the GSE206528 dataset.

Results: The MR analysis identified 263 genes associated with ED, with TRIP10 showing the highest degree, exhibiting an odds ratio (OR) of 0.58. Located on chromosome 7, TRIP10 plays a protective role in ED. Single-cell sequencing analysis revealed that TRIP10 is most highly expressed in endothelial cells and tissue stem cells, particularly in endothelial cells. Through PPI and single-cell analysis, we further identified potential causative genes, shedding light on their functions and their connection to the phenotype.

Conclusions: Our study found that among the 263 genes associated with ED, TRIP10 was strongly linked to a decreased risk of ED. These findings offer valuable insights for the personalized treatment of ED from a genetic perspective.

Introduction/background: Although surgery is less commonly selected as treatment for localized prostate cancer (PCa) as patients age, outcomes among older patients treated with radical prostatectomy remain unclear. The objective of this study was to compare survival across non-definitive therapy (NDT), radiotherapy, and radical prostatectomy (RP) among men older than 80 years old.

Materials and methods: Using the SEER-17 database, we identified patients ≥80 years at diagnosis with localized prostate cancer in 2000-2021 who were initially managed with NDT, radiotherapy, or RP. We compared overall (OS) and prostate cancer-specific survival (PCSS).

Results: We identified 53,437 patients with PCa≥80 years including 35,728 (68.2%) who underwent NDT, 15,906 (30.4%) treated with radiotherapy, and 736 (1.4%) with RP. The median age was 83 years (IQR: 81-85) and median PSA at diagnosis was 10.7 ng/mL (IQR: 6.7-19.9). Median OS was 66, 102 and 116 months for patients managed with NDT, radiotherapy, and RP, respectively (OS-P<0.01, PCSS-P<0.01). Cox regression revealed that compared to NDT, radiotherapy (OS-baseline adjusted hazard ratio: 0.48, 95% CI: 0.45-0.51, P<0.01; PCSS-baHR: 0.44, 95% CI: 0.38-0.51, P<0.01) and RP were associated with higher OS and PCSS (OS-baHR: 0.33, 95% CI: 0.24-0.46, P<0.01; PCSS-baHR: 0.19, 95% CI: 0.08-0.42, P<0.01).

Conclusion: These findings suggest that well-selected patients ≥80 years may experience favorable survival following RP.

Objectives: 2'-Hydroxyflavanone (2HF) has been recognized for its antitumor potential in recent years. In the past decade, the role of miRNAs in tumors has been gradually explored. Since natural compounds may regulate miRNA networks, our objective is to investigate the potential effects and mechanisms of 2HF in the treatment of bladder cancer (BCa) by targeting miRNAs.

Methods: Cell viability, tube formation, Transwell, western blotting and colony formation assays were used to evaluate the effects of 2HF on the viability and angiogenesis of BCa cells. The expression of miR-99a-5p and mTOR was detected via RT-qPCR and western blotting. A subcutaneous xenograft animal experiment was used to evaluate the tumor inhibition of 2HF in vivo. The binding of miR-99a-5p to mTOR was demonstrated via dual-luciferase reporting and RNA pull-down assays.

Results: 2HF inhibited the cell viability, angiogenesis, protein expression of VEGFa and Ki67 in T24 and 253J cells and protein expression of CD31 in HUVEC cells. Also, 2HF induced the upregulation of miR-99a-5p but the downregulation of mTOR expression. Additionally, the inhibitory effect of 2HF on tumor cells can be effectively rescued by silencing miR-99a-5p or overexpressing mTOR in vitro. Moreover, 2HF inhibited tumor growth in nude mice, in which it upregulated miR-99a-5p but suppressed mTOR expression in xenograft tissues. Mechanistically, miR-99a-5p can directly target the mRNA of mTOR by binding to its 3' untranslated region (3'-UTR) and then inhibiting the expression of mTOR.

Conclusions: 2HF inhibited BCa cell proliferation and angiogenesis by regulating the miR-99a-5p/mTOR/VEGFa axis, which may provide a novel treatment strategy and molecular mechanism for BCa treatment.

Ovarian squamous cell carcinoma [SCC] is a rare and aggressive malignancy that can mimic benign gynecological disorders, often leading to diagnostic delays and suboptimal management. Ureteral obstruction and subsequent hydroureteronephrosis due to extrinsic compression are atypical initial presentations of ovarian SCC. A 39-year-old female presented with nausea, vomiting, anuria, and bilateral hydroureteronephrosis, initially suspected to be endometriosis. Given the severity of acute kidney injury, emergent hemodialysis was initiated. Imaging demonstrated bilateral distal ureteral obstruction, necessitating percutaneous nephrostomy and subsequent referral for definitive management. Intraoperative findings revealed extensive fibrosis and adhesions, warranting left salpingo-oophorectomy and bilateral ureteroneocystostomy with double-J stent placement. Histopathological analysis confirmed ovarian SCC with direct ureteral invasion and hepatic metastases. Despite surgical intervention and palliative systemic therapy, the disease exhibited rapid progression, ultimately culminating in patient mortality. This case underscores the diagnostic complexities of ovarian SCC presenting with obstructive uropathy and highlights the necessity of maintaining a high index of suspicion for malignancy in patients with bilateral hydroureteronephrosis of unclear etiology. A timely, multidisciplinary approach integrating urological and oncological expertise is paramount in optimizing clinical outcomes.

Ureteral stent must be removed within a certain period, usually performed under the cystoscope. However, cystoscopic operations procedures carry risks such as urethral injury, hemorrhage, and infection. This study aimed to implement a cystoscope-free method for ureteral stent removal during the COVID-19 pandemic to mitigate the complications associated with cystoscopy, reduce the risk of cross-infection, and conserve medical resources and time. We retrospectively reviewed 33 patients who underwent ureteral stent removal at our institution between August and December 2022 during the COVID-19 pandemic. A simple device, consisting of an F6 or F8 gastric tube with the front end passing through a 3-0 Prolene line was utilized to extract the double-J stents without cystoscopic assistance. The gastric tube with the line was inserted into the urethra to drain urine from the bladder, saline was injected into the bladder, and the gastric tube was rotated with the line for 4-5 weeks, after which the stent tube was removed by gently pulling it outward. Perioperative characteristics assessed included operation time, pain score, stent removal success rate, postoperative complications, and reasons for stent removal failure. Among the 33 cases included in the study, 17 were males and 16 were females; 20 patients were older than 14 years while 13 were younger. Cystoscope-free stent removal was performed in all cases, with a success rate of 96.9% (32 patients), including 25 cases (78.1%) completed in one operation, four cases (12.5%) in two operations, and three cases (9.4%) in three operations. The mean extubation time was 4.3 ± 1.5 minutes, and the average pain score was 2.1 ± 0.7. No serious postoperative complications were noted. Cystoscope-free ureteral stent removal can be executed by a single physician, demonstrating simplicity, safety, effectiveness, and fewer complications. This method reduces the risk of cross-infection and conserves medical resources and time during the COVID-19 pandemic, making it suitable for both adults and children.

Objective: To investigate the expression of metabolism-related genes (MRGs) in kidney renal clear cell carcinoma (KIRC) and their association with patient prognosis, and to identify potential targets for intervention.

Methods: Bioinformatics methods were employed to mine the KIRC transcriptome data in The Cancer Genome Atlas Program (TCGA) database in order to identify MRGs that are aberrantly expressed in cancerous tissues. Subsequently, a prognostic risk score model was constructed and its predictive capacity was evaluated. Finally, the expression of prognostically relevant MRGs was validated using external datasets and KIRC clinical samples.

Results: A total of 789 differentially expressed MRGs associated with KIRC were screened, of which 465 genes were upregulated and 324 genes were downregulated, and finally 23 genes were screened to establish a risk score model. We found that the AUCs of the risk score model for predicting patients' 1-, 3- and 5-year overall survival (OS) were 0.804, 0.766 and 0.802, respectively. These findings suggest that the model has good predictive ability. A multifactorial Cox analysis revealed that 23 MRGs risk score was significantly associated with the overall survival of KIRC patients, and could therefore be used as an independent risk factor for the prognosis of KIRC patients (HR = 3.495, P < 0.001). Meanwhile, Kaplan-Meier analyses of the high-risk and low-risk groups indicated that the high-risk group exhibited a markedly inferior overall survival (OS) prognosis. The validation of clinical samples from KIRC patients and four external data sets (GSE36895, GSE40435, GSE53757 and GSE66272) demonstrated that KCNN4 and PLK1 were highly expressed in KIRC, whereas TEK, PLG, ANGPTL3, TFAP2A, ANK3, ATP1A1 and UCN exhibited low expression in KIRC.

Conclusion: Several MRGs are aberrantly expressed in KIRC, from which we screened 23 genes and constructed a MRGs prognostic risk model that can effectively predict the prognosis of KIRC patients and provide a new foundation for personalised diagnosis and treatment of KIRC.

Purpose: The estimated glomerular filtration rate (eGFR) has historically been calculated with a race-coefficient multiplier (RCM); however, the RCM has been broadly criticized as inaccurate and a potential contributor to exacerbating disparities. We evaluated the impact of the RCM on eGFR and examined the 30-day post-cystectomy complications in a muscle-invasive bladder cancer cohort.

Materials and methods: We retrospectively analyzed patients diagnosed with MIBC who underwent cystectomy in the ACS NSQIP database from 2006 to 2020 using CPT and ICD codes. The eGFR was computed using the Modification of Diet in Renal Diseases equation which has RCM = 1.212 for black patients. Using the race data field, patients were categorized into Black and non-Black. The eGFR cut-off of 60 mL/min/1.73 m² was chosen for patient stratification because it represents a key clinical threshold in the classification of chronic kidney disease and influences various care decisions such as chemotherapy choice. Subsequently, we examined the 30-day post-cystectomy cardiovascular and pulmonary (CV&P) complications in these patients stratified by their eGFR using descriptive statistics and a multivariable logistic regression model.

Results: The application of the RCM to estimate eGFR in the Black cohort increased the mean eGFR from 57.8 to 70.0 ml/min/1.73 m² (P = 0.001) which led to a 17.3% (45.6% vs 62.9%, P = 0.001) increase in the proportion of Black patients with eGFR≥60 ml/min/1.73 m². The rate of CV&P complications post-cystectomy among this group of 17.3% of patients in the Black cohort was 7.6% compared to a 4.3% complication rate among a non-Black cohort matched for similar eGFR for whom RCM was not applied (P = 0.06). Black patients in this RCM-dependent category of eGFR≥60 mL/min/1.73 m² had higher adjusted odds of developing 30-day post cystectomy CV&P complications compared to eGFR-matched non-Black patients (OR = 2.2, 95% CI = 1.13-4.31, P = 0.02).

Conclusion: In this study, we found that inclusion of RCM in the eGFR significantly increases the proportion of Black patients with eGFR≥60. This RCM might also be associated with higher post-cystectomy CV&P complications; therefore, future studies are needed to evaluate the implications of race-based algorithms on outcomes.

Background: Cancer stem cells (CSCs) have a powerful tumor initiation ability, which can promote the early dissemination of single disseminated tumor cells (DTCs), leading to tumor progression. SOX2, a pluripotent inducible transcription factor, is key to maintaining self-renewal and pluripotency of prostate cancer stem cells. However, there is a lack of comprehensive understanding of how SOX2 regulates DTCs dormancy and proliferation in the bone marrow microenvironment.

Methods and results: By constructing a mouse bone metastasis model to simulate the progression of prostate cancer with bone metastasis, the bone tissue immunofluorescence showed that SOX2 expression increased with the progression of prostate cancer in the bone marrow microenvironment. We validated this phenomenon with publicly available single-cell and transcriptome datasets and found that SOX2 is involved in multiple phenotypes associated with prostate cancer dormancy, proliferation, and invasion. Further, CCNE2, a potential target downstream of SOX2, was identified through multiple transcription factor databases and protein interaction networks.

Conclusion: The expression of SOX2 affects multiple phenotypes related to dormancy, proliferation and invasion of prostate cancer, and may indirectly activate the dormant prostate cancer cells through the downstream target gene CCNE2, thus affecting the progression and bone metastasis of prostate cancer.

Epithelial-mesenchymal transition (EMT) is a dynamic process of lineage plasticity in which epithelial cancer cells acquire mesenchymal traits, enabling them to metastasize to distant organs. This review explores the current understanding of how lineage plasticity and phenotypic reprogramming drive prostate cancer progression to lethal stages, contribute to therapeutic resistance, and highlight strategies to overcome the EMT phenotype within the prostate tumor microenvironment (TME). Emerging evidence reveals that prostate tumor cells can undergo lineage switching, adopting alternative growth pathways in response to anti-androgen therapies and taxane-based chemotherapy. These adaptive mechanisms support tumor survival and growth, underscoring the need for deeper insights into the processes driving prostate cancer differentiation, including neuroendocrine differentiation and lineage plasticity. A comprehensive understanding of these mechanisms will pave the way for innovative therapeutic strategies. Effectively targeting prostate cancer cells with heightened plasticity and therapeutic vulnerability holds promise for overcoming treatment resistance and preventing tumor recurrence. Such advancements are critical for developing effective approaches to prostate cancer treatment and improving patient survival outcomes.

Background: Nedylation and tumours are closely linked. The role of nedylation in bladder cancer (BCa) has rarely been reported and this study aims to explore its potential impact on the pathogenesis and progression of BCa.

Methods: Leveraging gene expression data from the TCGA database, this research employs the limma software package and WGCNA for gene module identification and analysis. Subsequent steps include the construction of a PPI network, the conduct of LASSO and univariate Cox regression analyses, and utilizing GSEA and single-cell sequencing to examine the influence of hub genes in bladder cancer-related biological pathways.

Results: The investigation revealed 11,361 genes with significant differential expression between normal and tumour tissues, and identified 1,500 hub genes through analysis. LASSO regression identified eight critical genes. Univariate Cox regression analysis revealed that COMMD9, GPS1, PSMB5, VHL, and WDR5 are independent prognostic factors for BCa. GSEA and single-cell sequencing highlight the potential of these genes to modulate immune responses and interactions between tumour and immune cells. Meanwhile, GSEA demonstrated that GPS1 can activate the NF-κB signalling pathway, leading to an increase in influenza virus polymerase activity.

Conclusion: This study identifies COMMD9, GPS1, PSMB5, VHL, and WDR5 as significant prognostic markers in BCa, thereby underscoring their roles in immune regulation and tumour-immune cell dynamics.