The advantages of en bloc resection of bladder tumors (ERBT) over transurethral resection of bladder tumors (TURBT) in terms of patient prognosis are not yet clear, and there are some technical limitations. We aimed to compare the tumor recurrence in non-muscle invasive bladder cancer (NMIBC) patients with tumor diameter ≥ 3 cm undergoing either TURBT or thulium laser ERBT. The patients included were those diagnosed with NMIBC based on pathological confirmation and underwent TURBT or modified thulium laser ERBT in the Department of Urology at Tongji Hospital from 2019 to 2024. The patients’ medical records were meticulously collected and postoperative follow-up was diligently conducted by trained personnel. Recurrence-free survival curves were generated utilizing the Kaplan–Meier method, and group comparisons were performed using the log-rank trend test. To minimize biases, we employed stratified survival analysis, alongside univariate and multivariate Cox regression analysis. This study included a total of 396 patients with NMIBC, with 214 undergoing TURBT and 182 undergoing ERBT. For all patients, there was no significant difference (P = 0.180) in RFS between the TURBT and ERBT groups. For patients with tumor diameter ≥ 3 cm, stratified analysis revealed that the RFS of the ERBT group was significantly better than that of the TURBT group (P = 0.033). However, in patients with tumor diameter < 3 cm, there was no significant difference (P = 0.150) between the two groups. Univariate (HR: 0.52, 95

We aimed to investigate the genomic and tumor microenvironmental (TME) profiles in non-muscle invasive bladder cancer (NMIBC) and explore potential predictive markers for Bacillus Calmette-Gu & eacute;rin (BCG) treatment response in high-risk NMIBC patients (according to European Association of Urology (EAU) risk stratification). 40 patients with high-risk NMIBC (cTis-T1N0M0) who underwent en bloc resection followed by BCG instillation were retrospectively enrolled. Surgical samples were subjected to Next Generation Sequencing (NGS) and multiplex immunofluorescence (mIF) assay. Genomic profiling revealed high prevalences of alterations in TERT (55%), KDM6A (32.5%), FGFR3(30%), PIK3CA (30%), TP53(27.5%) and ARID1A (20%). TME analysis showed different proportions of macrophages, NK cells, T cells subsets in tumoral and stromal compartment. Multivariate analysis identified TERT C228T and alteration in KDM6A as two independent factors associated with inferior RFS. The study comprehensively depicted the genomic and TME profiles in NMIBC and identified potential predictive biomarkers for BCG treatment.

Patients after kidney transplantation have a much higher risk of developing malignant tumors than the general population. And the native kidney is an organ relatively susceptible to malignant tumors after renal transplantation. However, the simultaneous development of bilateral renal tumors is very rare; especially the bilateral native kidneys harbor different pathological types of renal cell carcinoma (RCC). We report a case of a patient who developed malignant tumors in both native kidneys nearly 19 years after renal transplantation. This patient underwent bilateral laparoscopic radical nephrectomy, and postoperative pathological examination showed clear cell RCC on the left native kidney and papillary RCC on the right one. And the early detection and surgical treatment resulted in a good prognosis. The literature related to the diagnosis and treatment of bilateral RCC after renal transplantation is also reviewed.

Background: to evaluate the feasibility of texture analysis (TA) based on diffusion kurtosis imaging (DKI) in staging and grading bladder cancer (BC) and to compare it with apparent diffusion coefficient (ADC) and biparametric vesical imaging reporting and data system (VI-RADS). Materials and Methods: In this retrospective study, 101 patients with pathologically confirmed BC underwent MRI with multiple-b values ranging from 0 to 2000 s/mm2. ADC- and DKI-derived parameters, including mean kurtosis (MK) and mean diffusivity (MD), were obtained. First-order texture histogram parameters of MK and MD, including the mean; 5th, 25th, 50th, 75th, and 90th percentiles; inhomogeneity; skewness: kurtosis; and entropy; were extracted. The VI-RADS score was evaluated based on the T2WI and DWI. The Mann–Whitney U-test was used to compare the texture parameters and ADC values between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), as well as between low and high grades. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of each significant parameter and their combinations. Results: The NMIBC and low-grade group had higher MDmean, MD5th, MD25th, MD50th, MD75th, MD90th, and ADC values than those of the MIBC and the high-grade group. The NMIBC and low-grade group yielded lower MKmean, MK25th, MK50th, MK75th, and MK90th than the MIBC and high-grade group. Among all histogram parameters, MD75th and MD90th yielded the highest AUC in differentiating MIBC from NMIBC (both AUCs were 0.87), while the AUC for ADC was 0.86. The MK75th and MK90th had the highest AUC (both 0.79) in differentiating low- from high-grade BC, while ADC had an AUC of 0.68. The AUC (0.92) of the combination of DKI histogram parameters (MD75th, MD90th, and MK90th) with biparametric VI-RADS in staging BC was higher than that of the biparametric VI-RADS (0.89). Conclusions: Texture-analysis-derived DKI is useful in evaluating both the staging and grading of bladder cancer; in addition, the histogram parameters of the DKI (MD75th, MD90th, and MK90th) can provide additional value to VI-RADS.

经皮肾造瘘术和经皮肾镜取石术(percutaneous nephrolithotripsy,PCNL)并发脾脏损伤是一项罕见但可能致命的并发症,国外报道 20 余例[1-3],国内仅2 例报道[4-5].华中科技大学同济医学院附属同济医院收治 2 例经皮肾手术并发脾脏损伤的患者,现报告如下.

Recent studies suggest that cancer stemness drives the acquired drug resistance process in cancer therapy. The complementary information provided by multi-omics data can help us to gain a deeper understanding of this process. This study aims to elucidate the impact of cancer stemness on the frontline treatment of clear cell renal cell carcinoma (ccRCC). Consensus clustering based on stem/progenitor signatures refined 3 subgroups in 1,730 tumor samples. We identified master regulons that regulate cancer stemness phenotypes, including key transcription factors, DNA methyltransferases, and promoter methylation probes. In addition, we compared the clinicopathological traits, genomic heterogeneity, cancer hallmarks, tumor microenvironment (TME), and oncological prognosis of the stemness subgroups. Cancer stemness was correlated with reduced efficiency of immune checkpoint blockade therapy. Cancer stemness profoundly affects the prognosis and treatment outcome of ccRCC by increasing genomic instability, tumor-associated malignant events, and immunosuppressive factors. For clinical application, we established and validated a 243-gene signature from stem/progenitor-related genes to distinguish anti-PD-1 outcomes. Overall, this presented study suggested that cancer stemness leads to adaptive resistance to anti-PD-1 treatment in CD8+ T-infiltrated ccRCC and provides a new reference for strategy development to further improve immunotherapy response rates.

Accumulating evidence has suggested the impact of senescence on tumor progression, but no report has yet described how senescence shapes the tumor microenvironment of clear cell renal cell carcinoma (ccRCC). The objective of this study was to delineate the senescence features of ccRCC and its role in shaping the tumor microenvironment through a comprehensive analysis of multiple datasets, including 2,072 ccRCC samples. Unsupervised consensus clustering identified three senescence subtypes, and we found that the senescence-activated subtype survived the worst, even in the condition of targeted therapy and immunotherapy. The activated senescence program was correlated to increased genomic instability, unbalanced PBMR1/BAP1 mutations, elevated immune cell infiltration, and enhanced immune inhibitory factors (cancer-associated fibroblasts, immune suppression, immune exclusion, and immune exhaustion signaling). A senescence score based on nine senescence-related genes (i.e., P3H1, PROX1, HJURP, HK3, CDKN1A, AR, VENTX, MAGOHB, and MAP2K6) was identified by adaptive lasso regression and showed robust prognostic predictive power in development and external validation cohorts. Notably, we found that the senescence score was correlated to immune suppression, and the low-score subgroup was predicted to respond to anti-PD-1 therapy, whereas the high-score subgroup was predicted to respond to Sunitinib/Everolimus treatment. Collectively, senescence acted as an active cancer hallmark of ccRCC, shaped the immune microenvironment, and profoundly affected tumor prognosis and drug treatment response.

Bladder cancer is one of the most prevalent cancers. Despite recent advancements in bladder cancer therapy, new strategies are still required for improving patient outcomes, particularly for those who experienced Bacille Calmette–Guerin failure and those with locally advanced or metastatic bladder cancer. Oncolytic viruses are either naturally occurring or purposefully engineered viruses that have the ability to selectively infect and lyse tumor cells while avoiding harming healthy cells. In light of this, oncolytic viruses serve as a novel and promising immunotherapeutic strategy for bladder cancer. A wide diversity of viruses, including adenoviruses, herpes simplex virus, coxsackievirus, Newcastle disease virus, vesicular stomatitis virus, alphavirus, and vaccinia virus, have been studied in many preclinical and clinical studies for their potential as oncolytic agents for bladder cancer. This review aims to provide an overview of the advances in oncolytic viruses for the treatment of bladder cancer and highlights the challenges and research directions for the future.

International guidelines recommend repeat transurethral resection of bladder tumors (reTURB) for selected patients with high-risk non-muscle invasive bladder cancer to remove possible residual tumors, restage tumors and improve the therapeutic outcome. However, most evidence supporting the benefits of reTURB is from conventional TURB. The role of reTURB in patients receiving initial En bloc resection of bladder tumor (ERBT) is still unknown. PubMed, Embase, Web of Science, The Cochrane Library, and China National Knowledge Infrastructure (CNKI) were systematically searched. Finally, this systematic review and meta-analysis included twelve articles, including 539 patients. The rates of residual tumor and tumor upstaging detected by reTURB after ERBT were 5.9% (95%CI, 2.0%–11.1%) and 0.0% (95%CI, 0.0%–0.5%), respectively. Recurrence-free survival, tumor recurrence and progression were comparable between patients with and without reTURB after initial ERBT. The pooled hazard ratios of 1-year, 2-year, 3-year and 5-year recurrence-free survival were 0.74 (95%CI, 0.36–1.51; p = 0.40), 0.76 (95%CI, 0.45–1.26; p = 0.28), 0.83 (95%CI, 0.53–1.32; p = 0.43) and 0.83 (95%CI, 0.56–1.23; p = 0.36), respectively. The pooled relative risks of recurrence and progression were 0.87 (95%CI, 0.64–1.20; p = 0.40) and 1.11 (95%CI, 0.54–2.32; p = 0.77), respectively. Current evidence demonstrates that reTURB after ERBT for bladder cancer can detect relatively low rates of residual tumor and tumor upstaging and appears not to improve either recurrence or progression.

Background The Vesical Imaging-Reporting and Data System (VI-RADS) scoring system has been widely used to stage bladder cancer (BCa) since 2018. Purpose To describe the characteristics of cases with discordant T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) scores in patients with BCa and further verify the accuracy of the VI-RADS scoring system and the necessity of dynamic contrast-enhanced (DCE) sequence. Study Type Retrospective. Subjects A total of 106 patients (include 16.5% female) with bladder cancer. Sequence T2WI (fast spin echo), DWI (echo planer imaging), and DCE (gradient echo). Assessment Some cases are difficult to score according to the system, mainly when the T2WI (category 4) and DWI (category 2) sequence scores are discordant, termed the discordant group below. The complementary group will be termed concordant group. Each MRI sequence was reviewed respectively according to the 5-point VI-RADS scoring system by three observers. The diagnostic ability of sequences for evaluating muscle invasion by BCa was calculated using histopathology as the reference standards. Statistical Tests Receiver operating characteristic (ROC) curve, DeLong test, intraclass correlation coefficient. A P value of 0.05 or less was considered statistically significant. Results Fourteen cases (13.2%) had discordant VI-RADS scoring system. In the discordant group, the area under the ROC curve (AUC) of DCE was 0.875, while the T2WI and DWI showed limited diagnostic performance (AUCs = 0.50). In the concordant group, there was no significant difference in diagnostic efficacy between the overall VI-RADS (AUC: 0.950) and the combination of T2WI and DWI (AUC: 0.946) (P = 0.56). Among all patients, the AUC of overall VIRADS was 0.939 with a 3 or greater cutoff value. Data conclusion The DCE was crucial in the discordant group for evaluating muscle-invasiveness, while DCE may not be necessary for the concordant group. The VI-RADS scoring system performed with overall good diagnostic performance in evaluating muscle-invasiveness in BCa patients. Evidence Level 4 Technical Efficacy Stage 3

To evaluate the efficacy of repeat transurethral resection on restaging, preventing tumor recurrence and progression in high-risk non-muscle invasive bladder cancer patients who received initial en bloc resection. We reviewed retrospectively the clinical records of 330 consecutive patients who received en bloc resection for non-muscle invasive bladder cancer. Eligible patients with and without repeat transurethral resection were matched 1:1 by propensity score. Important covariates were balanced between the two groups. We compared the recurrence-free survival, progression-free survival, recurrence rate, and progression rate between groups. And the perioperative results regarding residual tumors and the safety of the repeat resection were also evaluated. Finally, there are 245 patients included in our analysis with a median follow-up duration of 19 months (range 3–50). Detrusor muscle presented in 244 (99.6

目的:评价基于CT影像三维重建的虚拟膀胱镜技术对于膀胱肿瘤病灶及正常组织的鉴别诊断价值.方法:检索PubMed、Embase、Cochrane、Medline数据库中关于CT影像、虚拟膀胱镜及膀胱癌的英文文献,由2名研究人员独立检索文献并提取数据,有异议时交由第三位研究人员进行评定.然后根据纳入排除标准筛选纳入研究的全文,最终根据QUADAS量表评价纳入文献的质量,采用Stata14.0软件和R语言(v4.1.1)进行数据处理和Meta分析,计算合并后的灵敏度及特异度,绘制受试者工作特征曲线并计算曲线下面积.结果:共纳入12篇文献,合计786个病灶.Meta分析显示,合并效应量后的灵敏度为0.96(95％CI:0.92～0.98),合并后的特异度为0.92(95％CI:0.82～0.97),合并后的基于CT影像的虚拟膀胱镜对于膀胱肿瘤病灶的诊断效能曲线下面积为0.98(95％CI:0.96～0.99).结论:基于CT影像三维重建的虚拟膀胱镜技术对于膀胱肿瘤病灶及正常组织或良性病变的诊断有较高的应用价值.

You have accessJournal of UrologyCME1 May 2022MP54-18 NOVEL THERAPEUTIC TARGETS AND POTENTIAL DRUGS FOR BCG INCURABLE NON-MUSCLE-INVASIVE BLADDER CANCER Zhou Peng, Hu Henglong, and Wang Shaogang Zhou PengZhou Peng More articles by this author , Hu HenglongHu Henglong More articles by this author , and Wang ShaogangWang Shaogang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002633.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is still a lack of alternative therapeutic drugs to cope with the dilemma of BCG treatment failure in non-muscle-invasive bladder cancer (NMIBC). This study aimed to expand the panel of druggable targets and drug candidates for BCG incurable NMIBC. METHODS: A detailed analysis of 345 BCG-treated NMIBC patients was conducted on transcriptomics and proteomics data. LASSO and stepwise regression were performed to establish a prognostic signature and validated its robustness in multiple datasets. The Pearson coefficients between CERES score and prognostic score were calculated to evaluate the dependence of bladder cancer cell lines on 2249 genes. Bladder cancer cell line expression profiles and drug sensitivity data (AUC values) for 1929 drug agents archived in the CTRP and PRISM databases were used as the training dataset, expression profiles of NMIBC patients were used as the test dataset to calculate its estimated AUC values by running a ridge regression model with 10-fold cross-validation. Spearman correlations between recurrence-risk scores and estimated AUC values were calculated and drugs with coefficients < -0.30 and more sensitive to the high-risk group were retained and validated in the CMap database. BCG was co-cultured with T24 at 10 CFU/cell until 80% of the cells died, and BCG was removed to restore cell growth to more than 50%, and the cycle operation exceeded 6 months to obtain the BCG resistant T24 cell line (BCG-R-T24). CCK8 and Flow Cytometry Assay on BCG-R-T24 were performed to test the therapeutic effect. RESULTS: A 14-gene prognostic signature was established and it outperformed the published signatures in predicting BCG treatment outcome (AUC >0.75 for recurrence, and >0.80 for progression, respectively). CERES score correlation analysis revealed that the proliferation of bladder cancer cell lines was highly dependent on TOP1, EED, HLA-A, PDE6D, PSMB1, PSMB4 and RRM2. After qPCR and Western blot confirmed their over-expression in BCG-R-T24, they were identified as potential therapeutic targets. Fourteen drugs were screened from the CTRP and PRISM databases, and CMap initially identified the therapeutic potential of clofarabine (targeting RRM2), irinotecan and SN-38 (targeting TOP1). CCK8 assay demonstrated the inhibition effect of clofarabine, irinotecan, and SN-38 on BCG-R-T24. Flow cytometry showed that the apoptotic ratio of BCG-R-T24 cells increased significantly under clofarabine, irinotecan, and SN-38 treatment. CONCLUSIONS: Clofarabine, irinotecan, and SN-38, especially clofarabine that targets RRM2, may have therapeutic value for NMIBC that underwent BCG treatment failure. Source of Funding: This presented study was supported by the National Natural Science Foundation of China, Youth Science Fund Project (Grant Number: 81700615) and the Chen Xiao-ping Foundation for The Development of Science and Technology of Hubei Province (No.202094). The funders have no role in designing and completing this study © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e934 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zhou Peng More articles by this author Hu Henglong More articles by this author Wang Shaogang More articles by this author Expand All Advertisement PDF downloadLoading ...

Hyperoxaluria is a risk factor for urolithiasis and can cause renal epithelial cell injury secondary to oxidative stress. Reactive oxygen species (ROS) produced during cell damage originate from different sources and play different roles. Here, we explored the potential sources of ROS production and investigated the role of ROS from various sources in oxalate-induced oxidative stress and cell injury in normal rat kidney-52 epithelial (NRK-52E) cells. Oxalate-induced injury was assessed by lactate dehydrogenase (LDH) release experiments. 2,7-dichlorodihydrofluorescein diacetate and mitoSOX Red were used to determine the intracellular and mitochondrial ROS (mtROS) production, respectively. The expression level of Nox4, Nox2, and p22 protein was detected by Western blotting to observe the effect of oxalate on nicotinamide adenine dinucleotide phosphate oxidase (NADPH) oxidase (Nox). Furthermore, a specific NADPH oxidase subtype inhibitor and targeted mitochondrial antioxidants were used to preliminarily identify the role of ROS from different sources in renal tubular epithelial cell injury induced by oxalate. We found that oxalate inhibited cell viability, induced LDH release, and prompted intracellular and mitochondrial ROS (mtROS) production. Oxalate also decreased the protein expression level of Nox4 and increased the protein expression level of p22. Mitochondria were also a source of ROS production. In addition, Nox2 inhibitor or mtROS scavenging prevented oxalate-induced cell injury, reversed by an inhibitor of Nox4/1. We concluded that ROS from different sources might play different roles in oxalate-induced renal tubular epithelial cell injury. We also identified new potential targets for preventing or alleviating oxalate-induced renal tubular epithelial cell injury.

Objective. Although the prognostic effect of statins on patients with prostate cancer (PCa) has been frequently evaluated, a consistent result is still lacking. We aimed to evaluate the association between statin use and mortality among patients with PCa after definite therapies. Methods. A systematic search of PubMed and other databases for cohort studies about the effect of statins on patients with PCa was performed until April 2022. Meta-analysis was performed using R software version 4.1.2. Results. 24 cohort studies involving 369, 206 participants were finally included. We found statin use significantly reduced the risk of prostate cancer-specific mortality (PCSM) with a pooled hazard ratio (pHR) = 0.76 (95% CI: 0.69–0.84, 18 studies), especially for postdiagnostic statin users: pHR = 0.81 (95% CI: 0.77–0.85) and patients who accepted androgen deprivation therapy (ADT): pHR = 0.69 (95% CI: 0.59–0.81). Statin use was also associated with a 24% reduction in the risk of all-cause mortality (ACM): pHR = 0.76 (95% CI: 0.68–0.85, 17 studies), especially for postdiagnostic statin users: pHR = 0.81 (95% CI: 0.78–0.85) and patients treated with ADT: pHR = 0.72 (95% CI: 0.63–0.82) or radiotherapy (RT): pHR = 0.68 (95% CI: 0.50–0.93). Conclusion. In conclusion, the use of statins could promote the prognosis of patients with PCa, especially for postdiagnostic users. For patients who received either ADT or radical prostatectomy (RP), statin use could decrease the PCSM. As for those who received either ADT or RT, statin use could decrease the ACM.

Aims: We aimed at exploring the role of nicotinamide adenine dinucleotide phosphate oxidase subunit 4 (Nox4) in the regulation of hypercalciuria-induced renal oxidative damage and crystal depositions.Results: High calcium activated Nox4 expression through protein kinase C (PKC). Downregulation of Nox4 expression attenuated hypercalciuria-induced osteoblast-associated protein expression, oxidative stress injury, and crystal deposition in rat kidneys of 1,25-dihydroxyvitamin D3 (VitD) urolithiasis model. Further, calcium-induced activation of mitogen-activated protein kinase (MAPK), overexpression of osteoblast-associated protein, oxidative stress injury, apoptosis, and calcium salt deposition in normal rat kidney epithelial-like (NRK-52E) cells were reversed by downregulating Nox4 expression but were enhanced by upregulating Nox4 expression in vitro. Moreover, calcium-induced increases of osteoblast-associated protein expression were attenuated by the c-Jun-N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) inhibitors.Innovation: Our results demonstrated the effect of Nox4 in the pathological process of kidney stones in in vitro and in vivo studies for the first time. Calcium aggravates renal oxidative stress injury and crystal deposition by activating the Nox4-related reactive oxygen species (ROS)-ERK/JNK pathway in the rat kidney. This study is expected to provide a new theoretical basis for the prevention and treatment of kidney stones.Conclusion: Nox4-derived ROS induced by calcium through PKC caused oxidative stress damage and apoptosis in renal tubular epithelial cells; in addition, Nox4-derived ROS induced by calcium mediated abnormal activation of the bone morphogenetic protein 2 (BMP2) signaling pathway through the MAPK signaling pathway, which induced renal tubular epithelial cells to transdifferentiate into osteoblast-like cells, resulting in the formation of a kidney stone.

BackgroundThe toll-like receptor 4 (TLR4) agonist, Bacille Calmette-Guérin, has exhibited gratifying effects in treating bladder cancer. The study aims to explore the expression pattern, prognostic value, and potential mechanism of TLR4 in bladder cancer.MethodsThe transcriptome file from the GSE13507 dataset in the Gene Expression Omnibus database and the promoter methylation file from the bladder cancer dataset in The Cancer Genome Atlas database were downloaded for analysis. The prognostic value of the TLRs was assessed by univariate Cox regression. Immunohistochemistry was applied to verify the expression of TLR4 in bladder cancer. The drug response is estimated through the R package “pRRophetic.” The CIBERSORT algorithm was carried out to estimate the infiltrating immune cells of samples. Gene Set Enrichment Analysis (GSEA) was performed to identify the pathways involved under varied TLR4 expression levels.ResultsTLR4 is decreased in tumor tissues compared with surrounding tumor tissues or normal tissue, which is also positively correlated to the overall survival rate (hazard ratio [HR] = 0.38) and cancer-specific survival rate (HR = 0.15) of patients with bladder cancer. Low expression of TLR4 is observed in tumors with malignant performance (high pathological grade, higher tumor stage, and progression). Patients with low TLR4 levels are more sensitive to gemcitabine rather than cisplatin. The promoter methylation level of TLR4 is positively associated with TLR4 expression (P < 0.001). The cg14629571 methylation site largely contributes to the overall methylation level. The CIBERSORT analysis shows that high TLR4 expression is associated with lower levels of plasma cells, M0 macrophages, and M1 macrophages. The GSEA results indicate that the TGF-β pathway and apoptosis are activated in high TLR4 bladder cancer, while G2M checkpoint and E2F targets pathways are enriched in low TLR4 bladder cancer.ConclusionThis research discusses the abnormal expression and prognostic value of TLR4 in bladder cancer. The TLR4 expression can effectively predict oncological outcomes and drug sensitivity of bladder cancer patients. TLR4 is also associated with infiltrating immune cell variation and cancer pathway dysregulation. The results provide a novel prognostic marker and potential drug targets for bladder cancer.

Background: Proteins are the most abundant component of kidney stone matrices and their presence may reflect the process of the stone's formation.Many studies have explored the proteomics of urinary stones and crystals.We sought to comprehensively identify the proteins found in kidney stones and to identify new, reliable biomolecules for use in nephrolithiasis research. Methods:We conducted bioinformatics research in November 2020 on the proteomics of urinary stones and crystals.We used the ClusterProfiler R package to transform proteins into their corresponding genes and Ensembl IDs.In each study we located where proteomic results intersected to determine the 20 most frequently identified stone matrix proteins.We used the Human Protein Atlas to obtain the biological information of the 20 proteins and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis to explore their biological functions.We also performed immunohistochemistry to detect the expression of the top five stone matrix proteins in renal tissue. Results:We included 19 relevant studies for analysis.We then identified 1,409 proteins in the stone matrix after the duplicates were removed.The 20 most-commonly identified stone matrix proteins were: S100A8, S100A9, uromodulin, albumin, osteopontin, lactotransferrin, vitamin K-dependent protein Z, prothrombin, hemoglobin subunit beta, myeloperoxidase, mannan-binding lectin serine protease 2, lysozyme C, complement C3, serum amyloid P-component, cathepsin G, vitronectin, apolipoprotein A-1, eosinophil cationic protein, fibrinogen alpha chain, and apolipoprotein D. GO and KEGG analysis revealed that these proteins were typically engaged in inflammation and immune response.Immunohistochemistry of the top five stone matrix proteins in renal tissue showed that the expression of S100A8, S100A9, and osteopontin increased, while uromodulin decreased in kidney stone patients.Albumin was rarely expressed in the kidney with no significant difference between healthy controls and kidney stone patients. Conclusion:Proteomic analysis revealed some common inflammation-related proteins in the kidney stone matrix.The role of these proteins in stone formation should be explored for their potential use as diagnostic biomarkers and therapeutic targets for urolithiasis.

Idiopathic hypercalciuria is an important risk factor for the formation of calcium-containing kidney stones. Matrix metalloproteinase-9 (MMP-9) is closely related to cell and tissue remodeling and is involved in ectopic tissue calcification. However, little is known about its role in kidney stone formation. In this study, we found that the expression of MMP-9 and that of osteoblastic-related proteins was increased in normal rat kidney epithelial-like (NRK-52E) cells following treatment with a high concentration of calcium, while the knockout or overexpression of MMP-9 could, respectively, significantly inhibit or upregulate the expression of osteoblastic-related proteins and calcium crystal deposition. In addition, apoptosis and calcium crystal deposition were significantly reduced in Sprague–Dawley rats with 1,25(OH)2D3-induced hypercalciuria following MMP-9 inhibitor I treatment. Furthermore, inhibiting reactive oxygen species (ROS) production or the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway significantly reduced calcium-induced MMP-9 expression and calcium crystal deposition. In summary, our results suggested that a high calcium concentration promotes epithelial–osteoblastic transformation and calcium crystal deposition in renal tubule cells by regulating the ROS/NF-κB/MMP-9 axis and identified a novel role for MMP-9 in regulating calcium-induced calcium crystal deposition in renal tubules.