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Overexpression of RNF2 Is an Independent Predictor of Outcome in Patients with Urothelial Carcinoma of the Bladder Undergoing Radical Cystectomy.

ABSTRACT: RNF2 (ring finger protein 2) is frequently overexpressed in several types of human cancer, but the status of RNF2 amplification and expression in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance is unclear. In this study, immunohistochemical analysis and fluorescence in situ hybridization (FISH) were used to examine the expression and amplification of RNF2 in 184 UCB patients after radical cystectomy. Overexpression of RNF2 was observed in 44.0% of UCBs and was found to significantly associate with shortened overall and cancer-specific survival (P < 0.001). In different subsets of UCBs, RNF2 overexpression was also identified as a prognostic indicator in patients with pT1, pT2, pN(-), and/or negative surgical margins (P < 0.05). Importantly, RNF2 overexpression together with pT status and surgical margin status provided significant independent prognostic parameters in multivariate analysis (P < 0.01). FISH results showed amplification of RNF2 in 8/79 (10.1%) of informative UCB cases. Additionally, RNF2 overexpression was significantly associated with RNF2 gene amplification (P = 0.004) and cell proliferation (P = 0.003). These findings suggested that overexpression of RNF2, as examined by immunohistochemical analysis, might serve as a novel prognostic biomarker and potential therapeutic target for UCB patients who undergo radical cystectomy.

SUBMITTER: Li XD

PROVIDER: S-EPMC4751429 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder.

Project description:BackgroundAn elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor outcome in various tumours. Its prognostic utility in patients with urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy (RC) is yet to be fully elucidated.MethodsA cohort of patients undergoing RC for UCB in a tertiary referral centre between 1992 and 2012 was analysed. Neutrophil-to-lymphocyte ratio was computed using complete blood counts performed pre-RC, or before neo-adjuvant chemotherapy where applicable. Time-dependent receiver operating characteristic curves were used to determine the optimal cutoff point for predicting recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The predictive ability of NLR was assessed using Kaplan-Meier analyses and multivariable Cox proportional hazards models. The likelihood-ratio test was used to determine whether multivariable models were improved by including NLR.ResultsThe cohort included 424 patients followed for a median of 58.4 months. An NLR of 3 was determined as the optimal cutoff value. Patients with an NLR⩾3.0 had significantly worse survival outcomes (5y-RFS: 53% vs 64%, log-rank P=0.013; 5y-CSS: 57% vs 75%, log-rank P<0.001; 5y-OS: 43% vs 64%, log-rank P<0.001). After adjusting for disease-specific predictors, an NLR ⩾3.0 was significantly associated with worse RFS (HR=1.49; 95% CI=1.12-2.0, P=0.007), CSS (HR=1.88; 95% CI=1.39-2.54, P<0.001) and OS (average HR=1.67; 95% CI=1.17-2.39, P=0.005). The likelihood-ratio test confirmed that prognostic models were improved by including NLR.ConclusionsNeutrophil-to-lymphocyte ratio is an inexpensive prognostic biomarker for patients undergoing RC for UCB. It offers pre-treatment prognostic value in addition to established prognosticators and may be helpful in guiding treatment decisions.

| S-EPMC4119979 | biostudies-literature

Preoperative plasma level of endoglin as a predictor for disease outcomes after radical cystectomy for nonmetastatic urothelial carcinoma of the bladder.

Project description:Elevated preoperative plasma level of endoglin has been associated with worse oncologic outcomes in various malignancies. The present large-scale study aimed to determine the predictive and prognostic values of preoperative endoglin with regard to clinicopathologic and survival outcomes in patients treated with radical cystectomy (RC) for nonmetastatic urothelial carcinoma of the bladder (UCB). We prospectively collected preoperative blood samples from 1036 consecutive patients treated with RC for UCB. Logistic and Cox regression analyses were undertaken to assess the correlation of endoglin levels with pathologic and survival outcomes, respectively. The AUC and C-index were used to assess the discrimination. Patients with adverse pathologic features had significantly higher median preoperative endoglin plasma levels than their counterparts. Higher preoperative endoglin level was independently associated with an increased risk for lymph node metastasis, ≥pT3 disease, and nonorgan confined disease (NOCD; all p < 0.001). Plasma endoglin level was also independently associated with cancer-specific and overall survival in both pre- and postoperative models (all p < 0.05), as well as with recurrence-free survival (RFS) in the preoperative model (p < 0.001). The addition of endoglin to the preoperative standard model improved its discrimination for prediction of lymph node metastasis, ≥pT3 disease, NOCD, and RFS (differential increases in C-indices: 10%, 5%, 5.8%, and 4%, respectively). Preoperative plasma endoglin is associated with features of biologically and clinically aggressive UCB as well as survival outcomes. Therefore, it seems to hold the potential of identifying UCB patients who may benefit from intensified therapy in addition to RC such as extended lymphadenectomy or/and preoperative systemic therapy.

| S-EPMC9293216 | biostudies-literature

Nutrition risk and assessment process in patients with bladder cancer undergoing radical cystectomy.

Project description:Malnutrition and depleted muscle stores adversely affect bladder cancer patients and contribute to poorer outcomes. These nutrition-related problems are often not addressed, in part because they are not being identified with screening and assessment tools. In this essay, we discuss validated nutrition screening and assessment tools such as the Patient-Generated Subjective Global Assessment; however, each healthcare team must decide on the one which will work best for their clinic. Patients with bladder cancer may be at risk for specific nutrient deficiencies which should be monitored and corrected to improve outcomes and overall health.

| S-EPMC7438246 | biostudies-literature

Prognostic value of vascular mimicry in patients with urothelial carcinoma of the bladder after radical cystectomy.

Project description:Vascular mimicry (VM) refers to the plasticity of aggressive cancer cells forming de novo vascular networks, which promoted tumor metastasis. The aim of this study was evaluate the impact of VM on recurrence-free survival (RFS) in urothelial carcinoma of the bladder (UCB). Records from 202 patients treated with radical cystectomy (RC) for UCB at Zhongshan Hospital between 2002 and 2014 were reviewed. The presence of VM was identified by CD31-PAS double staining. Positive VM staining occurred in 19.3% (39 of 202) UCB cases, and it was associated with increased risks of recurrence (Log-Rank p<0.001). VM was identified as an independent prognostic factor (p=0.002). In the cohort with MIBC, patients with VM negative got CSS benefit from the use of ACT (p = 0.048). As for lung metastasis, the combination of VM and TNM stage (AUC 0.792) showed a better prognostic value than TNM stage alone (AUC 0.748, p = 0.008) or VM alone (AUC 0.714, p = 0.023). Vascular mimicry could be a potential prognosticator for recurrence-free survival in patients with UCB after RC. Vascular mimicry seems to predict risk of developing lung metastases after RC. The presence of VM identified a subgroup of patients with MIBC who appeared to benefit from adjuvant chemotherapy.

| S-EPMC5342808 | biostudies-other

Prognostic Value of an Immunohistochemical Signature in Patients With Bladder Cancer Undergoing Radical Cystectomy.

Project description:BackgroundThis study aimed to assess the prognostic value of various diagnostic immunohistochemical (IHC) markers and develop an IHC-based classifier to predict the disease-free survival (DFS) of patients with bladder cancer undergoing radical cystectomy.MethodsIHC was performed on tumor specimens from 366 patients with transitional cell bladder cancer. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to develop a multi-marker classifier for predicting DFS of patients with bladder cancer. The Kaplan-Meier estimate was performed to assess DFS, and unadjusted and adjusted Cox regression models were used to identify independent risk factors to predict DFS of patients with bladder cancer.ResultsBased on the LASSO Cox regression model, nine prognostic markers were identified in the training cohort. Patients were stratified into low- and high-risk groups using the IHC-based classifier. In the training cohort, the 10-year DFS was significantly better in low-risk patients (71%) compared with high-risk patients (18%) (p < 0.001); in the validation cohort, the 10-year DFS was 86% for the low-risk group and 20% for the high-risk group (p < 0.001). Multivariable Cox regression analyses showed that the high-risk group based on the classifier was associated with poorer DFS adjusted by clinicopathological characteristics. Finally, a nomogram comprising the classifier and clinicopathological factors was developed for clinical application.ConclusionThe nine-IHC-based classifier is a reliable prognostic tool, which can eventually guide clinical decision making regarding treatment strategy and follow-up scheduling of bladder cancer.

| S-EPMC8027317 | biostudies-literature

The prognostic value of pretreatment of systemic inflammatory responses in patients with urothelial carcinoma undergoing radical cystectomy.

Project description:BackgroundSystemic inflammatory response (SIR) is important in the relationship between the tumour, the host, and outcome in cancer patients. However, limited data exist regarding the prognostic significance of SIR in bladder cancer. We investigate the utility of pretreatment SIR in patients with urothelial carcinoma undergoing radical cystectomy.MethodsThe study cohort consisted of 419 patients with a median follow-up of 37.7 months. The SIRs used for each described prognostic nomogram are consistent with previously published data: C-reactive protein, albumin, white cell count, neutrophil count, lymphocyte count, and platelet count. Primary end point was disease-specific survival (DSS) and overall survival (OS) after surgery. Cox regression models were used to determine the time to disease-specific and overall mortality. Multivariate regression coefficients of the predictors were used to develop nomograms for predicting 5-year DSS and OS probability.ResultsMultivariate Cox regression analyses revealed that albumin, lymphocyte count, and platelet count were significantly associated with a significantly increased risk for death from bladder cancer. The nomograms including each index were developed to predict the probability of 5-year DSS and OS after radical cystectomy. The C statistics were 77.8% and 77.3%, respectively, and exceeded the 2002 AJCC (72.0% and 70.3%, respectively). In the decision curve analyses, the nomograms including SIR demonstrated higher net benefit gains compared with the models without SIR.ConclusionsCellular components of SIR have better prognostic values compared with acute-phase protein in patients undergoing radical cystectomy for bladder cancer.

| S-EPMC4453653 | biostudies-literature

Prognostic value of preoperative hydronephrosis in patients with bladder cancer undergoing radical cystectomy: A meta-analysis.

Project description:BackgroundHydronephrosis is a common finding in patients with bladder cancer. The aim of the study was to appraise the prognostic value of preoperative hydronephrosis in bladder cancer patients undergoing radical cystectomy.MethodsWe conducted a literature search using PubMed and Embase databases in Aug 2018. Summary hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effects models. The primary endpoint was overall survival (OS). Secondary endpoints were cancer-specific survival (CSS) and recurrence-free survival (RFS).ResultsOverall, 13 studies published between 2008 and 2018 including 4,820 patients were selected for the meta-analysis. The age of bladder cancer patients ranged from 27 to 90.4 years, and the overall proportion of males was 72.5%. Preoperative hydronephrosis was reported in 27.4% of patients. The pooled HR was statistically significant for OS (HR, 1.36; 95% CI [1.20-1.55]) and CSS (HR, 1.64; 95% CI [1.33-2.02]), with no heterogeneity among the enrolled studies. Patients with bilateral hydronephrosis showed a poorer CSS compared to those with no hydronephrosis (HR 5.43, 95% CI [3.14-9.40]). However, there was no difference in CSS between no hydronephrosis and unilateral hydronephrosis groups (HR 1.35, 95% CI [0.84-2.14]). Despite a tendency towards poorer RFS (HR, 1.27; 95% CI [0.96-1.96]), the results demonstrated no significant association between presence of preoperative hydronephrosis and RFS after radical cystectomy.ConclusionThis meta-analysis indicates that preoperative hydronephrosis is significantly associated with poorer OS and CSS after radical cystectomy for patients with bladder cancer. Preoperative hydronephrosis has a stronger effect on CSS in patients with bilateral hydronephrosis. The presence of preoperative hydronephrosis not only predicts prognosis, but may also help to identify patients who benefit the most from neoadjuvant chemotherapy.

| S-EPMC6742405 | biostudies-literature

Decreasing Non-bladder-cancer Mortality After Radical Cystectomy.

Project description:Life expectancy is increasing in many parts of the world. Using proportional hazard models for competing risks, we investigated whether this increase has changed outcomes after radical cystectomy in a sample of 1419 consecutive patients treated between 1993 and 2018. During the observation period, the mean age and the proportion of patients with American Society of Anesthesiologists physical status class 3 or 4 increased, whereas the proportion of patients with heart disease decreased. Competing mortality (causes other than bladder cancer) decreased in all subgroups (hazard ratios [HRs] per year ranged from 0.931 to 0.963) and after controlling for increasing age (HRs ranged from 1.018 to 1.081). In an optimal model resulting from an analysis including age (HR per year 1.048, 95% confidence interval [CI] 1.027-1.070; p < 0.0001), comorbidity, tumor-related variables, body mass index, (neoadjuvant and adjuvant) chemotherapy and smoking status, the HR per increment for year of surgery was 0.928 (95% CI 0.886-0.973; p = 0.0019). The effect of year of surgery was greater than the decrease in competing mortality that may be expected with increasing life expectancy (4 yr for females, 6 yr for males).Patient summaryIn a review of data for 1993-2018, we found that death from other causes after removal of the bladder (radical cystectomy) for bladder cancer decreased over time. This decreasing trend might increase the age limit at which bladder cancer patients can benefit from radical cystectomy in the future.

| S-EPMC8317886 | biostudies-literature

The prognostic impact of perioperative blood transfusion on survival in patients with bladder urothelial carcinoma treated with radical cystectomy.

Project description:PurposeThe aim of our study was to assess the influence of perioperative blood transfusion (PBT) on survival outcomes following radical cystectomy (RC) and pelvic lymph node dissection (PLND).Materials and methodsWe reviewed and analyzed the clinical data of 432 patients who underwent RC for bladder cancer from 1991 to 2012. PBT was defined as the transfusion of allogeneic red blood cells during RC or postoperative hospitalization.ResultsOf all patients, 315 patients (72.9%) received PBT. On multivariate logistic regression analysis, female gender (p=0.015), a lower preoperative hemoglobin level (p=0.003), estimated blood loss>800 mL (p<0.001), and performance of neoadjuvant chemotherapy (p<0.001) were independent risk factors related to requiring perioperative transfusions. The receipt of PBT was associated with increased overall mortality (hazard ratio, 1.91; 95% confidence interval, 1.25-2.94; p=0.003) on univariate analysis, but its association was not confirmed by multivariate analysis (p=0.058). In transfused patients, a transfusion of >4 packed red blood cell units was an independent predictor of overall survival (p=0.007), but not in cancer specific survival.ConclusionsOur study was not conclusive to detect a clear association between PBT and survival after RC. However, the efforts should be made to continue limiting the overuse of transfusion especially in patients who are expected to have a high probability of PBT, such as females and those with a low preoperative hemoglobin level and history of neoadjuvant chemotherapy.

| S-EPMC4392029 | biostudies-literature

Urethrectomy at the time of radical cystectomy for non-metastatic urothelial carcinoma of the bladder: a collaborative multicenter study.

Project description:IntroductionThe optimal management of the urethra in patients planned for radical cystectomy (RC) remains unclear. We sought to evaluate the impact of urethrectomy on perioperative and oncological outcomes in patients treated with RC for non-metastatic urothelial carcinoma of the bladder (UCB).Materials and methodsWe assessed the retrospective data from patients treated with RC for UCB of five European University Hospitals. Associations of urethrectomy with progression-free (PFS), cancer-free (CSS), and overall (OS) survivals were assessed in univariable and multivariable Cox regression models. We performed a subgroup analysis in patients at high risk for urethral recurrence (UR) (urethral invasion and/or bladder neck invasion and/or multifocality and/or prostatic urethra involvement).ResultsA total of 887 non-metastatic UCB patients were included. Among them, 146 patients underwent urethrectomy at the time of RC. Urethrectomy was performed more often in patients with urethral invasion, T3/4 tumor stage, CIS, positive frozen section analysis of the urethra, and those who received neoadjuvant chemotherapy, underwent robotic RC, and/or received an ileal conduit urinary diversion (all p < 0.001). Estimated blood loss and the postoperative complication rate were comparable between patients who received an urethrectomy and those who did not. Urethrectomy during RC was not associated with PFS (HR 0.83, p = 0.17), CSS (HR 0.93, p = 0.67), or OS (HR 1.08, p = 0.58). In the subgroup of 276 patients at high risk for UR, urethrectomy at the time of RC decreased the risk of progression (HR 0.58, p = 0.04).ConclusionIn our study, urethrectomy at the time of RC seems to benefit only patients at high risk for UR. Adequate risk assessment of UCB patients' history may allow for better clinical decision-making and patient counseling.

| S-EPMC9236994 | biostudies-literature

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