Bladder Cancer Group Research Articles

Association between Zinc transporter genes ZIP11 rs11077654 polymorphism with bladder cancer risk in Chinese Han Population

ObjectiveTo study the association between Zinc transporter genes ZIP11 rs11077654 polymorphism with bladder cancer risk in Chinese Han Population. MethodsA total of 307 unrelated Chinese Han descent, including 139 bladder cancer patients as bladder cancer group and 168 healthy people as healthy control group were studied. The ZIP11 rs11077654 loci was analyzed by Polymerase Chain Reaction (PCR) and its relationship with bladder cancer was analyzed. ResultsThere were three kinds of genotypes in ZIP11 gene rs11077654 loci (CC, CA and AA). Our analysis presented that the CA genotype was not associated with bladder cancer risk when the CC genotype may be served as reference (OR, 1.355; 95% CI, 0.750–2.451; p = 0.313). We combined CA and AA genotypes as a dominant genetic model. There was no significant association with bladder cancer risk as well in the combined group (OR, 1.333; 95% CI, 0.758–2.343; p = 0.317). There was no significant association observed between the CA/AA genotypes and low-grade (OR, 0.900; 95% CI, 0.411–1.973; p = 0.793) or high-grade bladder cancer (OR, 0.675; 95% CI, 0.349–1.308; p = 0.243), and nor between the CA/AA genotypes and NMIBC (OR, 0.636; 95% CI, 0.334–1.213; p = 0.167) or MIBC (OR, 1.100; 95% CI, 0.478–2.531; p = 0.823). ConclusionThe rs11077654 of ZIP11 gene was not associated with bladder cancer in Chinese Han Population.

Clinical value of vascular endothelial growth factor and endostatin in urine for diagnosis of bladder cancer.

The aim of the study was to determine whether urinary VEGF and endostatin predict the presence of bladder cancer, and whether these noninvasive biomarkers provide clinically useful information in the bladder cancer patient as well. Voided urine samples were collected from 239 patients (109 bladder cancers, 81 urological disorders, 49 healthy controls). The urine levels of VEGF and endostatin were determined with the sandwich enzyme immunoassay technique. Urine levels of VEGF and endostatin were higher in patients with bladder cancer than those in patients with urological disorders and healthy controls (P <0.01). The difference between patients with urological disorder and healthy controls was significant only for VEGF (P <0.01). Urine level of VEGF was related to the tumor grade, and urine level of endostatin was related to tumor stage, tumor size and tumor number (P <0.05). The optimal cutoffs for VEGF and endostatin were calculated by the ROC curves as 860 pg/ml for VEGF, and 350 pg/ml for endostatin. The five-year survival rate was 60.0% in patients with low level of endostatin (<350 pg/ml) and 7.69% in patients with high level of endostatin (≥350 pg/ml) in the bladder cancer group. Patients with a high level of endostatin had a shorter survival time, whereas patients with a low level of endostatin had a longer survival time (P <0.05). Urine levels of VEGF and endostatin may be a clinically useful aid in the diagnosis of bladder cancer, and endostatin but not VEGF is a supplementary prognostic marker for predicting tumor progression.

'Very-low-risk' bladder tumours - a new entity?

To evaluate the homogeneity of the 'low-risk' bladder cancer group in an attempt to optimise follow-up protocols. Between June 1998 and December 2008, 211 patients (mean [sd] age of 66.7 [12.8]years) underwent transurethral resection of low-risk bladder cancer. Postoperative follow-up included cystoscopy at 3 and 12months after surgery, then annually for a total of 5years, and then annual ultrasonography indefinitely. After a median follow-up of 10years, 65 patients (30.7%) developed tumour recurrence and three (1.4%) stage progressions. In all, 84 patients (40%) had tumours of ≤1cm; these patients were significantly younger than patients with 1.1-3cm tumours (64.6 vs 68.3years, P = 0.03). Their 5-year recurrence-free survival rate was significantly higher (92% vs 70% in patients with larger tumours, P < 0.001). The median time to recurrence was 5.7years in patients with smaller tumours and 3.6years in patients with larger tumours (P = 0.03). Only 43.7% of the recurrences in patients with small tumours occurred within 5years, compared to 75.5% in patients with larger tumours. Patients with low-risk bladder cancer make an inhomogeneous group. They can be stratified according to tumour size. Patients with tumours of ≤1cm are younger, have lower risk of tumour recurrence, and most of their recurrences arise beyond the recommended 5-year surveillance period. It seems that these patients can be classified separately to a 'very-low-risk' group. Follow-up in these cases can be based on prolonged non-invasive evaluations.

Assessment of microsatellite instability for screening bladder cancer in high-risk population.

This study aims to determine the diagnostic efficacy of microsatellite markers for screening bladder cancer in population at high risk. A population of 200 people was screened for bladder cancer using a set of microsatellite markers. Urine samples were obtained from four different types of population groups - Group 1 (healthy population group), Group 2 (current smokers with a smoking history of more than 10 years), Group 3 (bladder cancer group), and Group 4 (bladder cancer group who were former smokers with a history of more than 10 years). Polymerase chain reaction (PCR) was performed to amplify microsatellite sequences at D9S63, D9S156, and D9S283. PCR products were separated on 1.8% agarose gel and were scanned using ultraviolet transilluminator. In Group 2 (high-risk population group, mainly current smokers with a history of more than 10 years), microsatellite alterations were found in 36 out of 50 people. We observed microsatellite alterations in 38 out of 50 people in Group 3 (bladder cancer group) and in 39 out of 50 people in Group 4 (bladder cancer group, mainly former smokers with a history of more than 10 years). The sensitivity of this test in Group 2, Group 3, and Group 4 was found to be 72%, 76% and 78%, respectively. The specificity of this test in each group was found to be 90%. Using these set of microsatellite markers, medium sensitivity and high specificity were reported for this test. The current findings suggest that a set of microsatellite markers (D9S63, D9S156, and D9S283) can be used to detect bladder cancer in high-risk population.

Spectrophotometric photodynamic detection involving extracorporeal treatment with hexaminolevulinate for bladder cancer cells in voided urine.

To evaluate the feasibility of hexaminolevulinate (HAL) for the photodynamic detection of cancer cells in voided urine. This study included 50 patients with bladder cancer that was confirmed histologically after transurethral resection (bladder cancer group) and 50 outpatients without a history of urothelial carcinoma or cancer-related findings (no malignancy group). One third of the voided urine samples were incubated with aminolevulinic acid (ALA-treated samples), one third were incubated with HAL (HAL-treated samples), and the remaining samples were incubated without treatment (untreated samples). For detecting cellular protoporphyrin IX levels, the intensity of the samples at the excitation wavelength of 405nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated or HAL-treated samples and the untreated samples at 635nm was calculated. HAL-induced fluorescence cytology (HFC) showed that the difference was significantly higher in patients with high-grade tumors than in those with low-grade tumors (p=0.0003) and the difference was significantly higher in patients with low-grade tumors than in those without a history of urothelial carcinoma or cancer-related findings (p=0.021). The areas under the receiver operating characteristic curves of ALA-induced fluorescence cytology (AFC) and HFC were 0.77 and 0.81, respectively. The AUC of HFC was significantly higher than that of AFC (p<0.0001). The overall sensitivity values for conventional cytology, AFC, and HFC were 49, 74, and 74%, respectively. The overall specificity values for AFC and HFC were 70 and 94%, respectively. Spectrophotometric photodynamic detection involving extracorporeal treatment with HAL for bladder cancer cells in voided urine showed high accuracy. This bladder cancer detection method is easy and cost-effective, and has the potential for clinical use.

Evaluation of NMP22 in bladder cancer patients sensitive to environmental toxins.

Bladder cancer (BC) is recognized as environmentally related. The interaction of environmental exposure to chemicals and genetic susceptibility seem to play important roles in BC development. In order to improve diagnosis and the recognition of BC risk, a group of markers which combine genetic susceptibility with detoxification and nuclear matrix protein (NMP22) is proposed. The aim of the study was to examine the utility of nuclear matrix protein (NMP22) as a diagnostic marker in BC in genetic susceptibility (NAT2 slow acetylators) combined with detoxification abilities (glutathione S-transferase GST and isoenzyme GST-π). The NMP22 level in urine, N-acetyltransferase 2 (NAT2) genotype and GST activity in hemolysate blood, as well as isoenzyme GST-π level, were determined in the urine and serum of 43 patients with BC and from 25 non-cancer controls. NMP22 and isoenzyme GST-π levels were measured by ELISA. The NAT2 genotype was examined in DNA isolated from whole blood using the PCR (Polymerase Chain Reaction) technique, while the activity of GST was determined with the spectrophotometric method. In the BC group, NMP22 (p = 0.005) concentration, GST-π (p = 0.003) in urine and GST (p = 0.009) activity in blood were statistically significantly higher than in the healthy controls. The majority of BC patients were slow acetylators (NAT2 genotype). A correlation between the level of nuclear matrix protein NMP22 and GST was found in all BC group (p = 0.007) and also slow acetylators (p = 0.0147). The results support the utility of a marker combination, which covers the genetic susceptibility to chemicals with the level of detoxification and nuclear matrix protein in BC patients. A relationship between NMP22 level in urine, GST level in blood and NAT2 genotype was observed. Also the isoenzyme GST-π in urine seems useful as a marker of BC.

Paraoxonase and arylesterase activity in bladder cancer.

Oxidative stress is the main pathogenetic mechanism in bladder cancer among many other causes. We aimed to investigate whether a potential relationship exists between bladder cancer and the activities of paraoxonase (PON1) and arylesterase (ARE) enzymes. The study included 56 patients with bladder cancer, and 57 healthy individuals. The relationships between enzyme activity and tumour grade, stage, muscular invasion and tumour size were evaluated. For statistical analysis, One-Sample Kolmogorov-Smirnov, Independent-T, ANOVA and Post-Hoc Bonferroni tests were used. Serum levels of PON1 and ARE enzymes, and total cholesterol were significantly lower in bladder cancer group. While other lipid parameters were similar in both the patient and the control groups. Levels of ARE were positively correlated with lipid parameters except for HDL cholesterol. Our results showed that decreased serum PON1 and ARE enzyme activities are related with tumour load and recurrence. Further studies with larger samples are needed to confirm predictive role of enzymatic activities of PON1 and ARE in the diagnosis and prognosis of bladder cancer.

Different expression patterns of histone H3K27 demethylases in renal cell carcinoma and bladder cancer.

UTX and JMJD3 are recently identified histone H3 lysine 27 (H3K27) demethylases. Many studies have shown aberrant H3K27 trimethylation (H3K27me3) levels widely exist in multiple cancers, and that altered H3K27me3 levels are correlated with tumorigenesis and tumor progression. To investigate expression patterns of UTX and JMJD3 genes in renal cell carcinoma (RCC) and bladder cancer and the relationship between gene expression and tumor development. Samples were collected from 35 patients with RCC and 21 patients with bladder cancer and qRT-PCR was performed. By comparing with adjacent normal tissues, the expression of JMJD3 (10/21 = 47.62%) and UTX (10/21 = 47.62%) were significantly upregulated in bladder cancer tissues and the expression of JMJD3 (15/35 = 42.86%) was significantly downregulated in RCC tissues. Stratified analyses revealed that upregulated expression of JMJD3 was significantly associated with poorly differentiated tumor nuclear grade (p= 0.005) and advanced clinical stage (p= 0.043) in the bladder cancer group, while downregulated expression of JMJD3 was significantly associated with advanced clinical stage (p= 0.045) and poorly differentiated tumor nuclear grade (p= 0.011) in the RCC group. These results suggest JMJD3 could be a hallmark and is involved in the development of RCC and bladder cancers. The potential role of H3K27 demethylases as biomarkers needs further investigations.

Association of B7-H4 gene polymorphisms in urothelial bladder cancer.

We aimed to study polymorphisms of the B7-H4 gene in order to evaluate a possible association in urothelial carcinoma, as it is highly expressed in cancer tissues. In this study B7-H4 gene rs10754339, rs10801935, and rs3738414 SNPs were studied by PCR-RFLP method in paraffin-embedded tumor specimens from 62 urothelial carcinoma patients and in a control group including 30 patients without bladder cancer. We detected that the rs10754339 polymorphism was more frequent in the cancer patients when compared with the control group (P < 0.05). Only the rs3738414 polymorphism showed a statistically significant difference in frequency between pathologic diagnostic groups. The rs10754339 AA genotype distribution was found to have a higher frequency whereas the rs3738414 AG genotype distribution was lower in the bladder cancer group (P < 0.05). None of the genotype distributions showed a significant difference from the control group for the rs10801935 polymorphism. We conclude that B7-H4 has the potential to be a useful prognostic marker in urothelial carcinoma.

The determination of serum and urinary endocan concentrations in patients with bladder cancer

Background Endocan (endothelial cell-specific molecule-1) is a proteoglycan and plays an important role in angiogenesis and inflammation. The aim of this study was to evaluate of serum and urinary concentrations of endothelial cell-specific molecule-1 in bladder cancer. Methods The study included 50 bladder cancer patients, 50 with urinary tract infection and 51 healthy volunteers. Serum and urinary endothelial cell-specific molecule-1 concentrations were measured with enzyme linked immunosorbent assay. Results In bladder cancer group, serum and urinary endothelial cell-specific molecule-1 concentrations were significantly higher than in the healthy subjects ( P = 0.003 and P < 0.0001). Urinary endothelial cell-specific molecule-1 concentrations in cases with urinary tract infection were higher than in healthy volunteers ( P = 0.002). There were no significant differences between bladder cancer and urinary tract infection groups in terms of serum and urinary endothelial cell-specific molecule-1 concentrations. Urinary endothelial cell-specific molecule-1 concentrations were higher than those of corresponding serum endothelial cell-specific molecule-1 concentrations ( P < 0.0001 for bladder cancer and urinary tract infection groups, P = 0.002 for healthy subjects). In bladder cancer group, there was a positive correlation between serum endothelial cell-specific molecule-1 and urinary endothelial cell-specific molecule-1 concentrations ( r = 0.32, P = 0.002). For serum endothelial cell-specific molecule-1, sensitivity and specificity were 50%, and 77%, and for urinary endothelial cell-specific molecule-1, 62%, and 71%, respectively. Conclusion Serum and urinary endothelial cell-specific molecule-1 concentrations increase in bladder cancer. This parameter also increases in serum and urine of cases with urinary tract infection. That urinary endothelial cell-specific molecule-1 values were higher than serum endothelial cell-specific molecule-1 values in all groups may be attributed to direct exfoliation of epithelial cells in bladder to urine.

Immunochemical and molecular assessment of urothelial neoplasms and aspects of the 2016 World Health Organization classification.

The new World Health Organization classification of tumours of the urinary system and male genital organs (4th edn) has several changes from previous versions, and was published in January 2016. New pathways have been discovered in the development of bladder cancer, and were included in this new classification. Guidance from the International Collaboration on Cancer Reporting (ICCR) helped to clarify open questions, in conjunction with the new classification. The histological groups of urothelial carcinoma evolved. Grading remained the same, despite controversy among European urologists. Substaging of pT1 tumours is recommended for the first time, and the ICCR has made recommendations on how to report this. Furthermore, worldwide advice has been published on the use of immunohistochemistry, and recommendations have been made to try to standardize the handling of bladder cancer from a histopathological point of view. At a molecular level, bladder cancer groups have been stratified, and an upcoming molecular classification permits a novel view of this malignancy. This review will try to summarize the most important changes.

The development of plasma pseudotargeted GC-MS metabolic profiling and its application in bladder cancer.

Bladder cancer (BC) is a fatal malignancy with considerable mortality. BC urinary metabolomics has been extensively investigated for biomarker discovery, but few BC blood metabolomic studies have been performed. Hence, a plasma pseudotargeted metabolomic method based on gas chromatography-mass spectrometry with selected ion monitoring (GC-MS-SIM) was developed to study metabolic alterations in BC. The analytical performance of the developed method was compared with that of a nontargeted method. The relative standard deviation (RSD) values of 89 and 70.7% of the peaks obtained using the pseudotargeted and nontargeted methods, respectively, were less than 20%. The Pearson correlations of 90.7 and 78.3% of the peaks obtained using the pseudotargeted and nontargeted methods, respectively, exceeded 0.90 in the linearity evaluation. Compared with the nontargeted method, the signal-to-noise ratios (S/N) of 97.9 and 69.3% of the peaks increased two- and fivefold, respectively. The developed method was fully validated, with good precision, recovery, and stability of the trimethylsilyl (TMS) derivatives. The method was applied to investigate BC. Significant increases in the contents of metabolites involved in, for example, the pentose phosphate pathway (PPP) and nucleotide and fatty acid synthesis were found in the high-grade (HG) BC group compared to the healthy control (HC) group. These differences imply that the activated PPP may regulate BC cell proliferation by promoting lipid and nucleotide biosynthesis and the detoxification of reactive oxygen species (ROS). These results illustrate that the plasma pseudotargeted method is a powerful tool for metabolic profiling. Graphical abstract The plasma pseudotargeted metabolic profiling suggested the metabolic alterations in bladder cancer (BC) and the significantly differential metabolites for BC discrimination.

Tissue and Plasma Endocan and Endoglin Levels in Patients with Bladder Cancer

Objective: In this study, we aimed to compare plasma endoglin and endocan levels between bladder cancer patients and the control group. The secondary aim of the study was to compare plasma and tissue endoglin and endocan levels between high grade and low grade bladder cancers. Methods: A total of 36 patients with bladder cancer and 20 patients as control group were included. Eight milliliters of peripheral venous blood sample was taken from both study and control group to determine plasma Endocan and Endoglin levels. A tissue sample of 0.5 cm3 was obtained by cystoscopy and resection of papillary lesion of bladder to determine tissue Endocan and Endoglin levels. Results were compared between bladder cancer and control group. Result: The mean plasma Endoglin levels were 10.2 (4.5-13.7) ng/mL in low grade bladder cancer, 14.6 (8.4-22.3) ng/mL in high grade bladder cancer and 8.8 (6.3-19.4) ng/mL in the control group. The mean plasma Endocan levels were 520.4 (346.9-647.6) ng/L in low grade bladder tumors; 728.5 (311.4-1518.1) ng/L in high grade bladder tumors and 479.9 (140.6-864.7) ng/L in the control group. Plasma Endoglin level of control group was significantly lower than bladder cancer group (p<0.001). Plasma Endocan level was not different between bladder cancer and control group (p=0.117). Conclusions: Plasma Endoglin level was up-regulated in bladder cancer patients whereas plasma Endocan level did not show any difference.

The Impact of Blue Light Cystoscopy with Hexaminolevulinate (HAL) on Progression of Bladder Cancer - A New Analysis.

Background: The International Bladder Cancer Group (IBCG) recently proposed a new definition of disease progression in non-muscle invasive bladder cancer (NMIBC), including change in T-stage, change to T2 or higher or change from low to high grade.Objective: To establish whether blue light cystoscopy with hexaminolevulinate (HAL) impacts the rate of progression and time to progression using the revised definition.Methods: An earlier long-term follow-up of a controlled Phase III study reported outcomes following blue light cystoscopy with HAL (255 patients) or white light (WL) cystoscopy (261 patients) in NMIBC patients. The data was re-analysed according to the new definition.Results: In the original analysis, after 4.5 years (median), eight HAL and 16 WL patients were deemed to have progressed (transition from NMIBC to muscle invasive bladder cancer, (T2-4)).According to the new definition, additional patients in both groups were found to have progressed: 31 (12.2%) HAL vs 46 (17.6%) WL (p = 0.085) with four (1.6%) HAL and 11 (4.2%) WL patients progressing from Ta to CIS. Time to progression was longer in the HAL group (p = 0.05).Conclusions: Applying the new IBCG definition there was a trend towards a lower rate of progression in HAL patients, particularly in those progressing from Ta to CIS. Time to progression was significantly prolonged. This suggests that patients should receive blue light cystoscopy with HAL rather than WL at resection. Adoption of the new definition could allow more patients at risk of progression to be treated appropriately earlier.

Definitions, End Points, and Clinical Trial Designs for Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group.

To provide recommendations on appropriate clinical trial designs in non-muscle-invasive bladder cancer (NMIBC) based on current literature and expert consensus of the International Bladder Cancer Group. We reviewed published trials, guidelines, meta-analyses, and reviews and provided recommendations on eligibility criteria, baseline evaluations, end points, study designs, comparators, clinically meaningful magnitude of effect, and sample size. NMIBC trials must be designed to provide the most clinically relevant data for the specific risk category of interest (low, intermediate, or high). Specific eligibility criteria and baseline evaluations depend on the risk category being studied. For the population of patients for whom bacillus Calmette-Guérin (BCG) has failed, the type of failure (BCG unresponsive, refractory, relapsing, or intolerant) should be clearly defined to make comparisons across trials feasible. Single-arm designs may be relevant for the BCG-unresponsive population. Here, a clinically meaningful initial complete response rate (for carcinoma in situ) or recurrence-free rate (for papillary tumors) of at least 50% at 6 months, 30% at 12 months, and 25% at 18 months is recommended. For other risk levels, randomized superiority trial designs are recommended; noninferiority trials are to be used sparingly given the large sample size required. Placebo control is considered unethical for all intermediate- and high-risk strata; therefore, control arms should comprise the current guideline-recommended standard of care for the respective risk level. In general, trials should use time to recurrence or recurrence-free survival as the primary end point and time to progression, toxicity, disease-specific survival, and overall survival as potential secondary end points. Realistic efficacy thresholds should be set to ensure that novel therapies receive due review by regulatory bodies. The International Bladder Cancer Group has developed formal recommendations regarding definitions, end points, and clinical trial designs for NMIBC to encourage uniformity among studies in this disease.

The relationship between functional promoter -94 ins/del ATTG polymorphism in NF-κ B1 gene and the risk of urinary cancer

A functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NF-κ B1 gene was reported to influence NF-κ B1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with the risk of urinary cancer, including renal cancer, bladder cancer and prostate cancer. TaqMan method was applied to genotype the NF-κ B1 -94 ins/del ATTG promoter polymorphism in three case-control studies: renal cell carcinoma group (1216 cases and 1588 controls), bladder cancer group (730 cases and 780 controls), and prostate cancer group (820 cases and 945 controls). Logistic regression was used to assess the association between the polymorphism and urinary cancer risk. The del/del genotype was detected to be associated with a statistically significant increased risk of bladder cancer when taking the ins/ins genotypes as reference (P < 0.001, adjusted odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.14-1.52). Furthermore, in bladder cancer, the same results were observed in the del/del genotype compared with the ins/ins + ins/del genotypes (P < 0.001, OR = 1.82, 95% CI = 1.41-2.35), and the del allele compared with the ins allele (P < 0.001, OR = 1.29, 95% CI = 1.12-1.49). However, no significant difference was observed in the associations between the NF-κ B1 polymorphism and the risk of renal cell carcinoma or prostate cancer in all kinds of models. In the Chinese population, the -94 ins/del ATTG polymorphism in NF-κ B1 promoter may contribute to the etiology of bladder cancer instead of renal cell carcinoma or prostate cancer.

Improved Noninvasive Bladder Cancer Diagnosis using Urine Sediments and Novel DNA Methylation Biomarker Panels.

Aberrant DNA methylation status early in carcinogenesis represents a potential indicator of tumor detection. We would like to establish a DNA methylation biomarker panel for bladder cancer detection in the research. Seven candidate genes with known cancer associations were selected for this study. The DNA methylation status of the candidate genes was analyzed by methylation-specific polymerase chain reaction assays to evaluate the relationship between bladder cancer and target gene methylation status in the urine sediments of participants. 112 bladder cancer patients, 10 healthy volunteers, and 17 glandular cystitis patients were enrolled. There were significant differences in the methylation status of p14ARF, RUNX3, RARβ, DAPK, and HPP1 between the healthy control, glandular cystitis, and bladder cancer groups (p = 0.027, p < 0.001, p < 0.001, p = 0.030 and p = 0.003, respectively). A panel composed of all five genes with significant methylation differences yielded an area under the receiver-operating characteristic curve (AUC) of 0.936 and had 98.21% sensitivity and 88.89% specificity, while a panel using just two of these genes (RUNX3 and RARP) yielded an AUC of 0.918 with 96.64% sensitivity and 88.89% specificity. Another panel of two genes (p14ARF and HPP1) had 100% specificity, but an AUC of 0.688 and 37.50% sensitivity. Using the urine of bladder cancer patients and healthy controls, we assessed several novel DNA methylation biomarker panels that demonstrated good bladder cancer detection capability. Based on the results of this study we recommend the RUNX3 and RARβ panel as the first choice for bladder cancer detection. In suspicious or difficult to diagnose cases, the p14ARF and HPP1 panel could be used as an additional diagnostic tool due to its high specificity.

Diagnostic Value of MicroRNAs for Urologic Cancers: A Systematic Review and Meta-Analysis.

MicroRNAs (miRNAs), particularly those extracted from the blood or tissues, have become the focus of urologic cancers research. However, the literature reviews on the accuracy of miRNA detection in urologic cancers have been inconsistent, leading us to perform this meta-analysis. Eligible studies were searched in PubMed and other databases. To calculate the pooled detection accuracy estimates, we used a bivariate random-effects meta-analysis model. According to the exclusion and inclusion criteria, 41 studies were included. Overall, the results showed sensitivity of 0.77 (95% CI: 0.74-0.80) and specificity of 0.76 (95% CI: 0.72-0.79), with an area under the SROC curve (AUC) of 0.83 (95% CI: 0.80-0.86). In addition, further subgroup analyses were also conducted. Firstly, the multiple miRNAs subgroup has significantly better diagnostic specificity than single miRNA subgroup among all these cancer types, while only bladder cancer (BC) and prostate cancer (PC) group with significantly greater diagnostic sensitivity with their multiple miRNA detection. Secondly, none of these cancer types showed significant differences on diagnostic sensitivity and specificity in their specimen and sample size subgroups. Thirdly, the diagnostic sensitivity between Asian (0.791, 95% CI: 0.748-0.827) and Caucasian (0.713, 95% CI: 0.666-0.756) in BC type was shown significant different with the P-value of 0.011. The results of our study suggested that miRNAs, particularly the multiple miRNAs, may play an important role in diagnosis and monitoring of the urologic cancers as superior biomarkers.

Quality of Life and Overall Survival in High Risk Patients After Radical Cystectomy With a Simple Urinary Derivation

ObjectiveTo evaluate quality of life (QoL) and overall survival after radical cystectomy with cutaneous ureterostomies for locally advanced bladder cancer in elderly patients with high surgical risk. MethodsFifty eight patients older than 74 years (mean age 80.6±4.3) with locally advanced bladder cancer (group A), underwent radical cystectomy and ureterocutaneous diversion. Patients completed the EORTC QLQC30 before and six months after surgery to assess functional, clinical, and QoL outcomes. The same evaluation was carried out in a control group (group B) of 29 patients (mean age 82.3±3.8 years), who had refused cystectomy. Questionnaires were also administered to patients of both groups who survived at least 20 months and 5 years. ResultsAll patients presented with an ASA score ≥3. Mean hospital stay was 15.1 days (±4.8) in group A and 23.5 days (±4.1) in group B. No intraoperative complications occurred in group A. Postoperative overall survival evaluated within 6 months in group A was 97% versus 79% in group B (P<.001).Relation between two groups at 6 months for Qol, functional and symptomatic items investigated showed in group A a statistically significant improvement for all parameters (P<.001). This advantage for patients belonging to group A still resulted evident at 20 months and 5 years.Short-term and 20 months overall survival resulted statistically significant in favour of group A (P<.001). ConclusionRadical cystectomy with cutaneous ureterostomy represents a valid alternative in elderly patients with invasive bladder cancer and high operative risk. Comparison between two groups showed a statistically significant difference for almost all the Qol related parameters and for short and medium term overall survival.

The expression and correlation of ZEB1 and E-cadherin in human bladder urothelial carcinoma

Objective To explore the expression, correlation and clinic-pathological characters of zinc finger E-box binding homeobox 1 (ZEB1) and E-cadherin in normal bladder tissues and bladder urothelial carcinoma(BUC). Methods Immunohistochemical staining was performed on paraffin embedded sections to detect the expression of ZEB1 and E-cadherin in 86 cases of BUC, diagnosed by pathology, between March 2008 and March 2011. Among them, 51 cases were male and 35 cases were female. The mean age was (64.1±10.2)years, range 36 to 72 years.40 cases were older than 65 years old, and 46 cases were less than 65 years old. The pathological classification included G1 in 28 cases, G2-G3 in 58 cases. The TNM classification showed that Ta-T1 stage in 34 cases, T2-T4 in 52 cases. Single lesion was found in 49 cases and multi lesion was found in 37 cases. 55 cases were primary lesion; the other 31 cases were diagnosed as tumor recurrence. Normal bladder mucosa was obtained from 16 patients with BPH. Their age ranged from 51 to 75 years old, mean (58.6±18.4)years old. Similar immunohistochemical staining about ZEB1 and E-cadherin was performed. The expression of ZEB1 and E-cadherin in different tissue and its relationship with the clinic pathological were further analyzed. Results The positive rate of ZEB1 in bladder cancer group (39.5%, 34/86) was significantly higher than that in normal bladder mucosa group(0, 0/16) (P<0.01). The positive rate of ZEB1 in high grade bladder cancer (G2-G3) was 48.3% (28/58), which was significant higher than that in low grade bladder cancer (G1) (21.4%, 6/28) (P<0.05); The positive rate of ZEB1 in muscle-invasive bladder cancer (T2-T4) was 51.9% (27/52), which was significant higher than that in non-muscle-invasive cancer (Ta-T1) (20.6%, 7/34) (P<0.01). The abnormal rate of E-cadherin expression in bladder cancer (61.6%, 53/86) was significantly lower than that in normal bladder mucosa (81.2%, 13/16) (P<0.01). The abnormal expression rate of E-cadherin in high grade bladder cancer (G2-G3) (53.4%, 31/58) was significantly lower than that in low grade bladder cancer (G1) (78.6%, 22/28)(P<0.05); The abnormal rate of E-cadherin expression in invasive bladder cancer (T2-T4) was 51.9% (27/52), which was lower than that in non-muscle invasive (Ta-T1) cancer (76.5%, 26/34) (P<0.05). In bladder cancer, there was a negative correlation between the abnormal expression of E-cadherin and positive expression of ZEB1 (r=0.247, P<0.05). Conclusion The expressions of ZEB1 and E-cadherin in bladder cancer were negatively correlated, which had high correlated with tumor grade and stage. Key words: Zinc finger E-box binding homeobox 1; E-cadherin; Bladder cancer; Immunohistochemistry