Disulfideptosis-associated lncRNAs reveal features of prognostic, immune escape, tumor mutation, and tumor malignant progression in renal clear cell carcinoma.

PURPOSE: Investigating the role of lncRNAs associated with the latest cell death mode (Disulfideptosis) in renal clear cell carcinoma, as well as their correlation with tumor prognosis, immune escape, immune checkpoints, tumor mutational burden, and malignant tumor progression. Searching for potential biomarkers and targets for renal clear cell carcinoma. METHODS: Downloaded the expression profile data and clinical data of 533 cases of renal clear cell carcinoma from the TCGA database, and randomly divided them into a test set (267 cases) and a validation set (266 cases). Based on previous research, 13 genes associated with Disulfideptosis were obtained. Using R software, lncRNAs with a differential expression that is related to the prognosis of renal clear cell carcinoma and associated with Disulfideptosis were screened out. After univariate Cox regression analysis, Lasso regression analysis, and multivariate Cox regression analysis, lncRNAs with independent predictive ability were obtained. A predictive risk model was established based on the risk scores. Verification was carried out between the obtained high-risk and low-risk groups and their subgroups (including Age, Gender, tumor mutational burden (TMB), tumor grading, and staging). Subsequently, a nomogram was established, and a calibration curve was generated for verification. Performed GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional enrichment analyses. Downloaded the values of Tumor Immune Dysfunction and Exclusion (TIDE) for all samples and calculated the difference between the high and low-risk groups. Selected human renal tumor cell lines (786-O, OS-RC-2, A-498, ACHN) and human renal cortex proximal tubule epithelial cell line (HK-2). The RNA expression levels of the above lncRNAs in each cell line were analyzed using RT-qPCR (Real-time Quantitative PCR Detecting System). Used siRNA (small interfering RNA) to knock down FAM225B in 786-O and OS-RC-2 cell lines, and then performed in vitro cell experiments to validate the functional characteristics of FAM225B. RESULTS: Our constructed predictive model includes 5 lncRNAs with an independent predictive ability (FAM225B, ZNF503-AS1, SPINT1-AS1, WWC2-AS2, LINC01338), which can effectively distinguish between patients in high and low-risk groups and their subgroups. The 1, 3, and 5-year AUC (Area Under the ROC Curve) values of the established nomogram are 0.756, 0.752, and 0.781, respectively. The 5-year AUC value is higher compared to other clinical characteristics (Age: 0.598, Gender: 0.488, Grade: 0.680, Stage: 0.717). After the knockdown of FAM225B, the proliferation, migration, and invasion abilities of renal cancer cell lines OS-RC-2 and 786-O all decreased. CONCLUSION: We have constructed and validated a prognostic model based on Disulfideptosis-associated lncRNAs. This model can effectively predict the high or low risk of patient prognosis and can distinguish the tumor cell mutational burden and immune escape capabilities among high-risk and low-risk patients. This predictive model can serve as an independent prognostic factor for renal clear cell carcinoma, providing a new direction for personalized treatment of patients with renal clear cell carcinoma.

GSDMB: A novel, independent prognostic marker and potential new therapeutic target in clear cell renal cell carcinoma.

Gasdermin (GSDM) family members are involved in numerous biological processes, including pyroptosis, as well as in the initiation and progression of various types of cancer. However, the specific role of GSDM genes in clear cell renal cell carcinoma (ccRCC) has yet to be fully clarified. The present study investigated the differential expression and genetic alterations GSDM genes, their effects on prognosis and immune modulation, and their functional enrichment in ccRCC. Several bioinformatics databases were used, including UALCAN, The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, Metascape, Tumor Immune Estimation Resource, GSCALite and cBioPortal. The results revealed that the expression levels of GSDMA, GSDMB, GSDMC and GSDMD were significantly upregulated in cancer tissues compared with those in paracancerous tissues in patients with ccRCC, whereas the expression of DFNB59 exhibited the opposite trend. The results were experimentally validated in patients with ccRCC, and it was confirmed that the expression levels of GSDMA, GSDMB, GSDMC, GSDMD and GSDME (DFNA5) were significantly enhanced, whereas (PJVK, DFNB59) expression was reduced. In addition, elevated GSDMB, GSDMD and DFNA5 expression levels were clearly associated with worse pathological characteristics of ccRCC, including a high pathological stage and high tumor grade. Furthermore, the high expression levels of GSDMB, GSDMC, GSDMD, DFNA5 and PJVK were shown to be associated with worse overall survival (OS) and progression-free interval in patients with ccRCC. Both univariate and multivariate analyses indicated that the expression of GSDMB was independently associated with the OS of patients with ccRCC. Additionally, a high mutation rate of GSDM genes (33%) was observed in patients with ccRCC, and GSDM gene mutations were also significantly associated with a poor OS in patients with ccRCC. Significant associations between GSDM genes and ccRCC immunoprofiling and drug sensitivity were also determined. In conclusion, the findings of the present study indicated that GSDMB, GSDMD and DFNA5 may be considered promising therapeutic agents and potential biomarkers for patients with ccRCC. Furthermore, GSDMB could act as an independent predictor for the OS of patients with ccRCC.

Trends in suicide mortality among prostate cancer survivors in the United States, 1975-2019.

BACKGROUND: Suicide was an important cause of death in prostate cancer. This study intended to investigate trends in suicide mortality among prostate cancer (PCa) survivors from 1975 to 2019 in the United States. METHOD: We identified PCa survivors from the Surveillance, Epidemiology, and End Results (SEER) program from January 1975 to December 2019. Standardized mortality rate (SMR) was calculated d to assess the relative risk of suicide in PCa survivors compared with the general men population. Poisson regression model was performed to test for trend of SMRs. The cumulative mortality rate of suicide was calculated to assess the clinical burden of suicide mortality. RESULTS: 7108 (0.2%) cases were death from suicide cause, and 2,308,923(65.04%%) cases recorded as dying from non-suicidal causes. Overall, a slightly higher suicide mortality rate among PCa survivors was observed compared with general male population (SMR: 1.15, 95%CI: 1.09-1.2). The suicide mortality rate declined significantly relative to the general population by the calendar year of diagnosis, from an SMR of 1.74(95%CI: 1.17-2.51) in 1975-1979 to 0.99(0.89-1.1) in 2015-2019 (Ptrend < 0.001). PCa survivors with aged over 84 years, black and other races, registered in registrations (including Utah, New Mexico, and Hawaii) failed to observe a decrease in suicide mortality (Ptrend > 0.05). The cumulative suicide mortality during 1975-1994 was distinctly higher than in 1995-2019(P < 0.001). CONCLUSION: The trend in suicide mortality declined significantly from 1975 to 2019 among PCa survivors compared with the general male population in the United States. Notably, part of PCa survivors had no improvement in suicide mortality, and additional studies in the future were needed to explore it.

The association between serum testosterone level and congestive heart failure in US male adults: data from National Health and Nutrition Examination Survey (NHANES) 2011-2016.

BACKGROUND: This study aimed to investigate the relationship between serum testosterone levels and the risk of congestive heart failure (CHF) in adult males. Previous research has suggested a potential link between serum testosterone and cardiovascular health, but the findings have been inconclusive. METHODS: This study was cross-sectional, and the data were obtained from the 2011-2016 cycle of the National Health and Nutrition Examination Survey (NHANES), which included a sample of 6,841 male participants. Serum testosterone levels were measured using a standardized assay, and CHF status was assessed through self-reporting. Covariates such as age, ethnicity, lifestyle factors, and health conditions were considered in the analysis. RESULTS: Among the participants, 242 individuals had a documented history of CHF. We observed a linear correlation between serum testosterone levels and CHF occurrence, with higher serum testosterone levels associated with a decreased risk of CHF (Q4 vs. Q1, OR = 0.29, 95% CI: 0.19-0.47, P < 0.001). After adjusting for confounding variables, multivariate analysis revealed that high serum testosterone levels remained significantly associated with a lower risk of CHF (OR: 0.47, 95% CI: 0.27-0.80, P = 0.01). Subgroup analysis indicated a significant association between high serum testosterone levels and reduced CHF risk in individuals over 50 years old. CONCLUSION: Our findings suggest that the serum testosterone level was positively associated with CHF in adult males. This study highlights the potential role of serum testosterone in cardiovascular health, particularly in older individuals. Further research is needed to elucidate the underlying mechanisms and explore the clinical implications of these findings.

Causal relationship between prostate cancer and 12 types of cancers: multivariable and bidirectional Mendelian randomization analyses.

BACKGROUND: Previous observational studies have shown an association between certain cancers and the subsequent risk of prostate cancer (PCa). However, the causal relationship between these cancers and PCa is still unclear. This study aimed to investigate the causal relationship between 12 common cancers and the risk of PCa. METHODS: We employed genome-wide association studies (GWAS) to perform forward and reverse Mendelian randomization (MR) within two-sample frameworks. Furthermore, we conducted multivariable MR analyses to investigate the relationships between different types of cancer. In addition, multiple sensitivity analysis methods were employed to assess the robustness of our findings. RESULTS: Our univariable MR analysis showed that genetically predicted hematological cancer was associated with a reduced risk of PCa (OR: 0.911, 95% CI 0.89-0.922, P = 0.03). Furthermore, MR analysis demonstrates that genetically predicted occurrence of thyroid gland and endocrine gland cancer also raised the risk of PCa (all P < 0.05). Multivariable analysis showed that thyroid gland cancer exhibited a higher incidence of PCa (OR: 1.12, 95% CI: 1.08-1.16, P = 0.008). In the reverse MR analysis, we found no significant inverse causal associations between PCa and 12 types of cancers. CONCLUSION: In summary, this study provided insights into the causal relationships between various types of cancer and PCa. Hematological cancer was suggested to associate with a lower risk of PCa, while thyroid gland cancer and endocrine gland cancer might increase the risk. These findings contribute to the understanding of genetic factors related to PCa and its potential associations with other cancers.

Molecular Expression and Prognostic Implications of Krüppel-Like Factor 3 (KLF3) in Clear Cell Renal Cell Carcinoma.

A major subtype of renal cancer is clear cell renal cell carcinoma (ccRCC). Krüppel-like factor 3 (KLF3) dysfunction is also revealed leading to poor prognosis in multiple cancer types. However, dysregulation and molecular dynamics of KLF3 underlying ccRCC progression still remains elusive. Here KLF3 gene and protein expressions in ccRCC were explored using data cohorts from The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and verified them in our patient cohort. Correlations of KLF3 expression with clinicopathological features, epigenetic modification, and immune microenvironment characteristics were further investigated. KLF3 was significantly down-regulated expressed in ccRCC tissues compared to adjacent normal controls. Adverse pathological parameters and poor prognosis were associated with lower expression of KLF3. Mechanically, KLF3 regulation was mainly attributed to CpG island methylation. KLF3-high expression subgroup was significantly enriched in cell signaling pathways most associated with EMT markers, angiogenesis, inflammatory response, apoptosis, TGF-ß, degradation of ECM, G2M checkpoint, and PI3K-AKT-mTOR. Based on GDSC database, KLF3 upregulation was identified to be associated with higher sensitivities towards PI3K-Akt-mTOR pathway inhibitors such as PI-103, PIK-93, and OSI-027. In addition, patients with down-regulated KLF3 expressions were found more sensitive towards Trametinib, Cetuximab, and Erlotinib. Collectively, our findings suggest that KLF3 may act as a suitable biomarker for prognosis prediction, tumor microenvironment (TME) phenotype identification, thereby helping ccRCC patients to make better therapeutic decisions.

Incidence and associated factors of developing second pelvic malignant neoplasms among prostate cancer patients treated with radiotherapy.

Objective: To identify risk factors of secondary pelvic malignant neoplasms (SPMNs) among prostate cancer (PCa) patients treated with radiotherapy. Simultaneously, population-based data were used to validate the high risk of SPMNs in PCa patients with radiotherapy. Materials and methods: We identified male patients diagnosed with PCa (localized and regional) as the first primary cancer and pelvic malignant neoplasm (including bladder and rectal cancer) as secondary cancer from Surveillance, Epidemiology, and End Results database (1975-2020). An external validation cohort was obtained from the First Affiliated Hospital of Nanchang University. The Fine-Gray competing risk regression and Poisson regression were utilized to evaluate the risk of SPMNs development. Poisson regression was also performed to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to assess the overall survival (OS) of patients with SPMNs. Results: 89397 PCa patients treated with radiotherapy were enrolled. We identified associated factors of SPMNs, including age at diagnosis, race, year of diagnosis, marital status, radiation strategy and latency. In the multivariable competing risk regression model and Poisson regression model, a significantly higher risk of SPMNs development was observed in patients over 50 years(P<0.05), white patients(P<0.001), unmarried patients and treated with brachytherapy combined with external beam radiotherapy or brachytherapy(P<0.05). Patients treated with radiotherapy had a higher bladder and rectal cancer incidence than the general population. Patients who developed SPMNs showed poorer OS. Conclusion: We identified several risk factors associated with SPMNs and confirmed a relatively higher incidence of bladder and rectal cancer among PCa patients with radiotherapy. These results help tailor treatment and surveillance strategies.

Assessing the prognostic impact of prostatic urethra involvement and developing a nomogram for T1 stage bladder cancer.

PURPOSE: To investigate prognostic values of prostatic urethra involvement (PUI) and construct a prognostic model that estimates the probability of cancer-specific survival for T1 bladder cancer patients. METHOD AND MATERIALS: We investigated the national Surveillance, Epidemiology, and End Results (SEER) database (2004-2015) to get patients diagnosed with T1 bladder cancer. An external validation cohort was obtained from the First Affiliated Hospital of Nanchang University. The Kaplan-Meier method with the log-rank test was applied to assess cancer-specific survival (CSS) and overall survival (OS). Moreover, the propensity score matching (PSM) and multivariable Cox proportional hazard model were performed. All patients were randomly divided into the development cohort and validation group at the ratio of 7:3. The performance of the model was internally validated by calibration curves and the concordance index (C-index). RESULTS: The PUI group had a lower survival rate of both CSS and overall survival OS before and after PSM when compared to non-involved patients (All P < 0.05). Multivariate analysis revealed a poor prognosis in the PUI group for cancer-specific mortality (CSM) and all-cause mortality (ACM) analyses before and after PSM (All P < 0.05). Seven variables, including age, surgery, radiotherapy, tumour size, PUI, and marital status, were incorporated in the final nomogram. The C-index in the development cohort was 0.715 (0.711-0.719), while it was 0.672 (0.667-0.677) in the validation group. Calibration plots for 3- and 5-year cancer-specific survival showed good concordance in the development and validation cohorts. CONCLUSIONS: PUI was an independent risk factor of ACM and CSM in T1 bladder cancer patients. In addition, a highly discriminative and precise nomogram that predicted the individualized probability of cancer-specific survival for patients with T1 bladder cancer was constructed.

Development, comparison, and validation of four intelligent, practical machine learning models for patients with prostate-specific antigen in the gray zone.

Purpose: Machine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier for patients in the prostate-specific antigen gray zone are to be developed and compared, identifying valuable predictors. Predictive models are to be integrated into actual clinical decisions. Methods: Patient information was collected from December 01, 2014 to December 01, 2022 from the Department of Urology, The First Affiliated Hospital of Nanchang University. Patients with a pathological diagnosis of prostate hyperplasia or prostate cancer (any PCa) and having a prostate-specific antigen (PSA) level of 4-10 ng/mL before prostate puncture were included in the initial information collection. Eventually, 756 patients were selected. Age, total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), fPSA/tPSA, prostate volume (PV), prostate-specific antigen density (PSAD), (fPSA/tPSA)/PSAD, and the prostate MRI results of these patients were recorded. After univariate and multivariate logistic analyses, statistically significant predictors were screened to build and compare machine learning models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier to determine more valuable predictors. Results: Machine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier exhibit higher predictive power than individual metrics. The area under the curve (AUC) (95% CI), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score of the LogisticRegression machine learning prediction model were 0.932 (0.881-0.983), 0.792, 0.824, 0.919, 0.652, 0.920, and 0.728, respectively; of the XGBoost machine learning prediction model were 0.813 (0.723-0.904), 0.771, 0.800, 0.768, 0.737, 0.793 and 0.767, respectively; of the GaussianNB machine learning prediction model were 0.902 (0.843-0.962), 0.813, 0.875, 0.819, 0.600, 0.909, and 0.712, respectively; and of the LGBMClassifier machine learning prediction model were 0.886 (0.809-0.963), 0.833, 0.882, 0.806, 0.725, 0.911, and 0.796, respectively. The LogisticRegression machine learning prediction model has the highest AUC among all prediction models, and the difference between the AUC of the LogisticRegression prediction model and those of XGBoost, GaussianNB, and LGBMClassifier is statistically significant (p < 0.001). Conclusion: Machine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier algorithms exhibit superior predictability for patients in the PSA gray area, with the LogisticRegression model yielding the best prediction. The aforementioned predictive models can be used for actual clinical decision-making.​.

The value of EYA1/3/4 in clear cell renal cell carcinoma: a study from multiple databases.

There is evidence from multiple studies that dysregulation of the Eyes Absent (EYA) protein plays multiple roles in many cancers. Despite this, little is known about the prognostic significance of the EYAs family in clear cell renal cell carcinoma (ccRCC). We systematically analyzed the value of EYAs in Clear Cell Renal Cell Carcinoma. Our analysis included examining transcriptional levels, mutations, methylated modifications, co-expression, protein-protein interactions (PPIs), immune infiltration, single-cell sequencing, drug sensitivity, and prognostic values. We based our analysis on data from several databases, including the Cancer Genome Atlas database (TCGA), the Gene Expression Omnibus database (GEO), UALCAN, TIMER, Gene Expression Profiling Interactive Analysis (GEPIA), STRING, cBioPortal and GSCALite. In patients with ccRCC, the EYA1 gene was significantly highly expressed, while the expression of EYA2/3/4 genes showed the opposite trend. The level of expression of the EYA1/3/4 gene was significantly correlated with the prognosis and clinicopathological parameters of ccRCC patients. Univariate and multifactorial Cox regression analyses revealed EYA1/3 as an independent prognostic factor for ccRCC, establishing nomogram line plots with good predictive power. Meanwhile, the number of mutations in EYAs was also significantly correlated with poor overall survival (OS) and progression-free survival (PFS) of patients with ccRCC. Mechanistically, EYAs genes play an essential role in a wide range of biological processes such as DNA metabolism and double-strand break repair in ccRCC. The majority of EYAs members were related to the infiltration of immune cells, drug sensitivity, and methylation levels. Furthermore, our experiment confirmed that EYA1 gene expression was upregulated, and EYA2/3/4 showed low expression in ccRCC. The increased expression of EYA1 might play an important role in ccRCC oncogenesis, and the decreased expression of EYA3/4 could function as a tumor suppressor, suggesting EYA1/3/4 might serve as valuable prognostic markers and potential new therapeutic targets for ccRCC.

Trends in cause of death among patients with renal cell carcinoma in the United States: a SEER-based study.

BACKGROUND: Renal cell carcinoma (RCC) survival has improved due to recent developments in RCC treatment. Therefore, other co-morbid conditions may have a more critical role. This study aims to explore the common causes of death in patients with RCC to improve the management and survival of RCC. METHOD: We used the Surveillance, Epidemiology, and End Results (SEER) (1992-2018) database to get patients with RCC. We calculated the percentage of total deaths of six kinds of the cause of death (COD) and the cumulative incidence of death for each selected cause over survival time. The joinpoint regression was utilized to present the trend of mortality rate by COD. RESULTS: We enrolled 107,683 cases with RCC. RCC was the leading cause of death in patients with RCC [25376(48.3%)], followed by cardiovascular diseases [9023(17.2%)], other cancers [8003 (15.2%)], other non-cancer diseases [4195 (8%)], non-disease cause [4023 (7.7%)], and respiratory diseases [1934 (3.6%)]. The proportion of patients who died of RCC decreased gradually over survival time, and this value decreased from 69.71% in 1992-1996 to 38.96% in 2012-2018. The non-RCC cause mortality rate showed an increasing trend, whereas a slight decrease was observed in RCC specific mortality rate. The distribution of such conditions varied across different patient populations. CONCLUSION: RCC was still the primary COD of patients with RCC. However, non-RCC cause death was increasingly important among RCC patients in recent two decades. Cardiovascular disease and other cancers were crucial co-morbidities that required significant attention in the management of RCC patients.

Upregulation of MTHFD2 is associated with PD­L1 activation in bladder cancer via the PI3K/AKT pathway.

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) has been implicated in the etiology of various human malignant tumors; however, its exact role in bladder cancer (BC) remains to be explored. Through reverse transcription­quantitative PCR, western blotting and immunohistochemistry detection of BC tissue, combined with The Cancer Genome Atlas (TCGA) database analysis, the present study demonstrated that MTHFD2 was upregulated in BC tissues. MTHFD2 expression in patients with BC was frequently associated with worse prognosis, tumor immune cell infiltration and programmed death­ligand 1 (PD­L1) expression. Subsequently, using short hairpin RNA, the expression levels of MTHFD2 were knocked down in BC cell lines, and the results revealed that the tumor cell proliferation and colony formation abilities of cells were greatly reduced, as determined by Cell Counting Kit 8 and colony formation assays, as was the expression of PD­L1, as determined by western blotting. These findings were also confirmed in a xenograft nude mouse model. Simultaneously, it was revealed that abnormal expression of MTHFD2 was closely associated with the PI3K/AKT signaling pathway in both RNA­sequencing and TCGA datasets. This observation was verified in vitro by detecting the protein expression levels of PI3K and AKT by western blotting. The activation of PI3K and AKT was enhanced in BC cells (T24) following stimulation with 740Y­P, a PI3K activator, and cellular activities and PD­L1 expression levels were restored. Finally, it was demonstrated that the MTHFD2 levels were correlated with chemosensitivity to traditional BC chemotherapeutic agents and various PI3K/AKT­targeted drugs, as determined by analyzing the Genomics of Drug Sensitivity in Cancer database. Overall, the present findings revealed that upregulation of MTHFD2 was associated with PD­L1 activation in BC via the PI3K/AKT signaling pathway, suggesting that it could be a promising marker of chemotherapy and immunotherapy for BC.

Pathological diagnostic nomograms for predicting malignant histology and unfavorable pathology in patients with endophytic renal tumor.

Purpose: To develop and validate nomograms for pre-treatment prediction of malignant histology (MH) and unfavorable pathology (UP) in patients with endophytic renal tumors (ERTs). Methods: We retrospectively reviewed the clinical information of 3245 patients with ERTs accepted surgical treatment in our center. Eventually, 333 eligible patients were included and randomly enrolled into training and testing sets in a ratio of 7:3. We performed univariable and multivariable logistic regression analyses to determine the independent risk factors of MH and UP in the training set and developed the pathological diagnostic models of MH and UP. The optimal model was used to construct a nomogram for MH and UP. The area under the receiver operating characteristics (ROC) curves (AUC), calibration curves and decision curve analyses (DCA) were used to evaluate the predictive performance of models. Results: Overall, 172 patients with MH and 50 patients with UP were enrolled in the training set; and 74 patients with MH and 21 patients with UP were enrolled in the validation set. Sex, neutrophil-to-lymphocyte ratio (NLR), R score, N score and R.E.N.A.L. score were the independent predictors of MH; and BMI, NLR, tumor size and R score were the independent predictors of UP. Single-variable and multiple-variable models were constructed based on these independent predictors. Among these predictive models, the malignant histology-risk nomogram consisted of sex, NLR, R score and N score and the unfavorable pathology-risk nomogram consisted of BMI, NLR and R score performed an optimal predictive performance, which reflected in the highest AUC (0.842 and 0.808, respectively), the favorable calibration curves and the best clinical net benefit. In addition, if demographic characteristics and laboratory tests were excluded from the nomograms, only the components of the R.E.N.A.L. Nephrometry Score system were included to predict MH and UP, the AUC decreased to 0.781 and 0.660, respectively (P=0.001 and 0.013, respectively). Conclusion: In our study, the pathological diagnostic models for predicting malignant and aggressive histological features for patients with ERTs showed outstanding predictive performance and convenience. The use of the models can greatly assist urologists in individualizing the management of their patients.

Renal Pseudoaneurysms after Flexible Ureteroscopy and Holmium Laser Lithotripsy: A Case Report.

Background: Flexible ureteroscopy (FURS) and holmium laser lithotripsy is considered one of the most minimally invasive and safe surgical methods for the treatment of renal calculi. Renal pseudoaneurysm is a rare complication after FURS holmium laser lithotripsy. We report a case of renal pseudoaneurysm after FURS and holmium laser lithotripsy and review the relevant literature to analyze the possible etiology and summarize the treatment. Case presentation: A 29-year-old male with a 2-year history of diabetes was admitted to the hospital because of right back pain for 5 days. A doppler ultrasound demonstrated bilateral renal calculi with bilateral mild hydronephrosis. The patient underwent one-stage right FURS and holmium laser lithotripsy and bilateral ureteral stent implantation. The urine was clear on the second day after the operation, and he was discharged from the hospital. Due to severe gross hematuria, he had to be hospitalized 28 days after the operation. A CT scan showed multiple blood clots in the right renal pelvis and bladder. An emergency blood transfusion and removal of the bladder blood clots and bilateral double J tubes were performed. His urine was clear for one week, and he was discharged from the hospital. He was hospitalized again 47 days after the operation because of fever and hematuria. A CT scan demonstrated blood clots in the bladder and right renal pelvis. Angiography showed a pseudoaneurysm in a small branch of the right renal artery, and hematuria stopped after selective renal artery embolization with microcoils. Conclusion: FURS and holmium laser lithotripsy is safe, but we should be aware of the possibility of renal artery pseudoaneurysms (RAP). Through careful operation during the surgery, avoiding kidney injury, reducing intrarenal pressure and controlling the time of operation may prevent the occurrence of this complication. Vascular embolization is the first choice for the treatment of pseudoaneurysms.

Trends in Incidence, Mortality, and Survival of Penile Cancer in the United States: A Population-Based Study.

Purpose: The aim of this study is to investigate the trends in incidence and mortality, and explore any change in survival of penile cancer in the United States. Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2018) utilizing the SEER Stat software. The joinpoint regression was used to analyze the secular trend of incidence and incidence-based mortality (IBM) stratified by age, race, and summary stage. The 5-year relative survival rate was also calculated. Result: The age-adjusted rates of penile cancer patients were 0.38 (0.37-0.39) and 0.21 (0.2-0.21) for overall incidence and IBM, respectively. The 5-year relative survival rates were 67.7%, 66.99%, and 65.67% for the calendar periods of 2000-2004, 2005-2009, and 2010-2014, respectively. No significant changes in incidence by era were observed from 2000 to 2018 [annual percentage change (APC) = 0.5%, p = 0.064]. The IBM rate of penile cancer showed an initial significant increase from 2000 to 2002 (APC = 78.6%, 95% CI, -1.7-224.6) followed by a deceleration rate of 4.6% (95% CI, 3.9-5.3) during 2002 to 2018. No significant improvement in 5-year relative survival was observed. The trends by age, race, and summary stage in incidence and IBM were significantly different. Conclusion: This study, using population-level data from the SEER database, showed an increasing trend in IBM and no significant improvement in the 5-year relative survival rate. Meanwhile, the incidence of penile cancer exhibited a relatively stable trend during the study period. These results might be due to the lack of significant progress in the treatment and management of penile cancer patients in the United States in recent decades. More efforts, like increasing awareness among the general population and doctors, and centralized management, might be needed in the future to improve the survival of this rare disease.

LncRNA ITGB2-AS1 promotes the progression of clear cell renal cell carcinoma by modulating miR-328-5p/HMGA1 axis.

Clear cell renal cell carcinoma (ccRCC) is the most common histologic subtype of renal cell carcinoma and long non-coding RNAs (lncRNAs) play important roles in the progression of ccRCC. In this study, we aim to explore the potential function of ITGB2-AS1 in ccRCC progression and its underlying molecular mechanism. We first explored the association between ITGB2-AS1 expression level and ccRCC prognosis. We found that the expression level of ITGB2-AS1 was significantly higher in ccRCC tumor and cell lines, and highly expressed ITGB2-AS1 was also associated with a poorer prognosis. Consistently, silencing ITGB2-AS1 inhibited proliferation, promoted apoptosis in ccRCC cell lines, and curbed the tumorigenesis in the Xenograft model, reduced tumorigenesis in a xenograft tumor growth model. We further identified and confirmed the miRNA miR-328-5p as a target of ITGB2-AS1, and miR-328-5p negatively regulated the expression of HMGA1 protein. The anti-tumor effect of silencing ITGB2-AS1 could be partially rescued by inhibiting miR-328-5p activity or overexpressing HMGA1, indicating that ITGB2-AS1 promotes the survival and progression of ccRCC by modulating miR-328-5p/HMGA1 axis. Collectively, our data demonstrated that ITGB2-AS1 expression level is positively correlated with the survival and tumorigenesis of ccRCC. As a target of ITGB2-AS1, miR-328-5p seems to function as a tumor-suppressor, and the oncogenic effect of ITGB2-AS1 is partially mediated via the miR-328-5p/HMGA1 axis.

Photoselective vaporization of the prostate with GreenLight 120-W laser versus transurethral resection of the prostate for benign prostatic hyperplasia: a systematic review with meta-analysis of randomized controlled trials.

The aim of this study is to assess the overall efficacy and safety of photoselective vaporization of the prostate (PVP) with GreenLight 120-W laser versus transurethral resection of the prostate (TURP) for treating patients of benign prostate hyperplasia (BPH) with lower urinary tract symptoms (LUTS). We performed a literature search of The Cochrane Library and the electronic databases, including Embase, Medline, and Web of Science. Manual searches were conducted of the conference proceedings, including European Association of Urology and American Urological Association (2007 to 2012). Outcomes reviewed included clinical baseline characteristics, perioperative data, complications, and postoperative functional results, such as postvoid residual (PVR), international prostate symptom score (IPSS), quality of life (QoL), and maximum flow rate (Qmax). Six randomized controlled trials (RCTs) were enrolled. Three hundred and forty-seven patients undergone 120-W PVP, and 350 patients were treated with TURP in the RCTs. There were no significant differences for clinical characteristics in these trials. In perioperative data, catheterization time and length of hospital stay were shorter in the PVP group. However, the operation time was shorter in the TURP group. Capsular perforation, blood transfusion, clot retention, and macroscopic hematuria were markedly less likely in PVP-treated subjects. The other complications between PVP and TURP did not demonstrate a statistic difference. There were no significant differences in QoL, PVR, IPSS, and Qmax in the 1, 3, 6, 12, and 24 months of postoperative follow-up. There was no significant difference at postoperation follow-up of functional outcomes including IPSS, PVR, Qmax, and QoL between the TURP-treated subjects and PVP-treated subjects. Owing to a shorter catheterization time, reduced hospital duration and less complication, PVP could be used as an alternative and a promising minimal invasive surgical procedure for the treatment of BPH.