Prognosis Of Bladder Cancer Patients Research Articles

Long noncoding RNA BLACAT2 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis.

The prognosis for bladder cancer patients with lymph node (LN) metastasis is dismal and only minimally improved by current treatment modalities. Elucidation of the molecular mechanisms that underlie LN metastasis may provide clinical therapeutic strategies for LN-metastatic bladder cancer. Here, we report that a long noncoding RNA LINC00958, which we have termed bladder cancer-associated transcript 2 (BLACAT2), was markedly upregulated in LN-metastatic bladder cancer and correlated with LN metastasis. Overexpression of BLACAT2 promoted bladder cancer-associated lymphangiogenesis and lymphatic metastasis in both cultured bladder cancer cell lines and mouse models. Furthermore, we demonstrate that BLACAT2 epigenetically upregulated VEGF-C expression by directly associating with WDR5, a core subunit of human H3K4 methyltransferase complexes. Importantly, administration of an anti-VEGF-C antibody inhibited LN metastasis in BLACAT2-overexpressing bladder cancer. Taken together, these findings uncover a molecular mechanism in the lymphatic metastasis of bladder cancer and indicate that BLACAT2 may represent a target for clinical intervention in LN-metastatic bladder cancer.

Impact of body mass index on the oncological outcomes of patients with upper and lower urinary tract cancers treated with radical surgery: A multi-institutional retrospective study.

To evaluate the impact of body mass index (BMI) on the oncological outcomes of urothelial carcinoma (UC) patients. We retrospectively analyzed data from 818 patients with upper tract urothelial cancer (UTUC) and bladder cancer (BC) who were treated with radical nephroureterectomy (RNU) or radical cystectomy (RC) between 1990 and 2015 at six different institutions in Japan. Patients with distant metastasis at diagnosis and those who received neoadjuvant therapies were excluded, leaving 727 eligible patients (UTUC: n = 441; BC: n = 286). Patients were classified into four groups according to World Health Organization BMI criteria: underweight (BMI <18.5 kg/m2 ), normal weight (BMI 18.5-25kg/m2 ), overweight (BMI 25.1-30kg/m2 ), and obese (BMI >30kg/m2 ). Overweight UTUC and BC patients achieved significantly better cancer-specific survival (CSS) than the other three groups. However, obese UTUC and BC patients had significantly worse CSS than the other three groups (UTUC: P = 0.031; BC: P = 0.0019). Multivariate analysis of BC patients demonstrated that obesity was an independent predictor of unfavorable CSS (hazard ratio [HR] = 7.47; P = 0.002) and that being underweight was an independent predictor of favorable CSS (HR = 0.37; P = 0.029). However, BMI was not a prognostic factor for CSS in UTUC patients according to multivariate analysis. Obesity was an independent predictor of BC patients requiring RC. Conversely, being underweight was associated with a favorable prognosis for BC patients. However, BMI was not an independent prognostic factor in patients with upper urinary tract cancer.

MicroRNA-374a Inhibits Aggressive Tumor Biological Behavior in Bladder Carcinoma by Suppressing Wnt/β-Catenin Signaling

Background/Aims: microRNA (miR)-374a plays a crucial role in cancer progression by promoting the metastasis and proliferation of various types of malignant tumors. Because its role in bladder cancer is unknown, we investigated whether miR-374a affects the progression of bladder cancer and studied the underlying mechanism. Methods: The Cancer Genome Atlas was used to analyze the clinical relevance of miR-374a. Quantitative PCR, western blotting, and luciferase and immunofluorescence assays were used to detect the expression patterns, downstream targets, and function of miR-374a in bladder cancer cells. Apoptosis was evaluated by flow cytometry after cisplatin treatment. Results: Via in silico analysis, low levels of miR-374a were associated with poor prognosis in bladder cancer patients with distant metastasis. WNT5A was a direct target of miR-374a in two bladder cancer cell lines. miR-374a mimic abrogated the metastatic potential and invasiveness of bladder cancer cells via WNT5A downregulation in both T24 and TCCSUP human bladder cancer cells; the opposite was observed with miR-374a inhibitor. In addition, miR-374a treatment reduced the phosphorylation and nuclear translocation of β-catenin. Cisplatin treatment significantly increased the apoptosis rate. Expression levels of cancer stemness-related proteins were reduced in miR-374a mimic-pretreated cells. Conclusion: Lower expression of miR-374a is associated with poor prognosis and miR-374a improves tumor biological behavior in bladder cancer cells, suggesting that miR-374a might be a novel small-molecule therapeutic target.

Long non-coding RNA expression in bladder cancer.

The advent of novel high-throughput sequencing methods has facilitated identification of non-coding RNAs with fundamental roles in cellular biological and pathological conditions. A group of these consisting of at least 200 nucleotides are called long non-coding RNAs (lncRNAs). Their participation in the pathogenesis of cancer has been highlighted in recent years. Bladder cancer, one of the most prevalent cancers worldwide, exhibits altered expression levels of several lncRNAs. Several in vitro and in vivo studies have assessed the effects of silencing RNAs on cancer cell phenotypes and in vivo tumor growth. For instance, in vitro studies have shown that nuclear paraspeckle assembly transcript1 (NEAT1), promoter of CDKN1A antisense DNA damage-activated RNA(PANDAR) and metastasis-associated lung adenocarcinoma transcript1(MALAT1) have oncogenic effects while Maternally expressed 3 (MEG3) and BRAF activated non-coding RNA (BANCR) are tumor suppressors. Analysis of these data will help to identify a panel of lncRNAs that can be potentially used for both early detection and prognosis in bladder cancer patients. Here, we review the roles of several lncRNAs in the oncogenesis, tumor suppression, early detection, and prognosis of bladder cancer.

LncRNA SNHG5 is associated with poor prognosis of bladder cancer and promotes bladder cancer cell proliferation through targeting p27.

Long non-coding RNAs (lncRNAs) have been identified as critical regulators in tumorigenesis. In our present study, we measured the level of small nucleolar RNA host gene 5 (SNHG5) in bladder cancer (BC) tissues and cell lines, and the correlation of the level of SNHG5 with clinicopathological features and prognosis of BC patients was analyzed. Reverse transcription-quantitative polymerase chain reaction was performed to determine the level of SNHG5 in the BC tissues and cell lines. The Kaplan-Meier method was used to analyze the long-term survival outcomes. MTT and colony formation assays were applied to assess the influence of SNHG5 on cell proliferation ability. Flow cytometry was used to measure the function of SNHG5 on cell cycle and apoptosis rate. SNGH5 was found upregulated in BC tissues and cell lines and a high level of SNGH5 was correlated with a poor prognosis. Silencing SNHG5 inhibited the proliferation ability of BC cells and such a function was attributed to its influence on cells cycle and apoptosis. Our findings imply that SNHG5 was upregulated in BC tissues and played an important role in BC progression and may be a potential therapeutic target for BC patients.

Identification of a three miRNA signature as a novel potential prognostic biomarker in patients with bladder cancer.

There is not a good biomaker that is closely related to survival time for bladder cancer(BLCA), The aim of the study is to identify a miRNA signature that could predict prognosis in BLCA patients according to the data from The Cancer Genome Atlas (TCGA). a total of 377 BLCA patients were finally enrolled in the study. The three miRNA signature was identified by Multivariate Cox proportional hazards analyses that common clinical variables were controled. The three microRNA signature showed greater predicting prognosis capacity for predicting 5-year survival in BLCA with an AUC of 0.664, 0.681 and 0.668 in Train set, Test set and Total set respectively. Furthermore, there was a significant difference between high score and low score in Total set(P=3e-05), Test set(P=0.00435) and Train set(P=0.00143), respectively. Therefore, these results provided a new prospect for prognostic biomarker of BLCA.

Long non-coding RNA XIST promotes cell growth and metastasis through regulating miR-139-5p mediated Wnt/β-catenin signaling pathway in bladder cancer.

Bladder cancer is one of the most common urological malignancy all over the world. Recently, long non-coding RNA (lncRNA) XIST has been identified as an oncogenic gene in several type of cancers. However, the expression level and functional role of XIST in bladder cancer remain largely unknown. In the present study, we found that XIST was significantly up-regulated in bladder cancer tissues and cell lines, and was correlated with poor prognosis of bladder cancer patients. Furthermore, XIST knockdown significantly inhibited bladder cancer cell growth and metastasis in vitro and tumor growth in vivo. We also demonstrated that XIST acted as a competing endogenous RNA for miR-139-5p and repression of miR-139-5p could restore the inhibitory effects on bladder cancer cells induced by XIST shRNA. In addition, we identified that Wnt1 was a direct target of miR-139-5p, and XIST played the oncogenic role in bladder cancer by activating the Wnt/β-catenin signaling pathway. Taken together, our study suggested that lncRNA XIST may serve as a prognostic biomarker and a potential therapeutic target for bladder cancer.

MP98-20 THE ROLE OF TOLL-LIKE RECEPTOR 4 IN BLADDER CANCER PROGRESSION.

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology V1 Apr 2017MP98-20 THE ROLE OF TOLL-LIKE RECEPTOR 4 IN BLADDER CANCER PROGRESSION. Tomoya Fukawa, Terumichi Shintani, Kei Daizumoto, Tomoharu Fukumori, Masayuki Takahashi, and Hiro-omi Kanayama Tomoya FukawaTomoya Fukawa More articles by this author , Terumichi ShintaniTerumichi Shintani More articles by this author , Kei DaizumotoKei Daizumoto More articles by this author , Tomoharu FukumoriTomoharu Fukumori More articles by this author , Masayuki TakahashiMasayuki Takahashi More articles by this author , and Hiro-omi KanayamaHiro-omi Kanayama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3085AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Toll-like receptors (TLRs) play important roles in immune response and have been reported that expression levels of these molecules were related to prognoses of several kinds of cancer. It has been reported that the expression level of TLR4 is reduced in bladder cancer. However, the role of TLR4 in bladder cancer is still unclear. The aim of this study is to clarify the effects of TLR4 expression on prognosis of bladder cancer patients and to elucidate its underlying mechanisms. METHODS To evaluate the effects of TLR4 expression on prognosis, we analyzed the clinical outcomes of 95 patients with bladder cancer and also conducted immunohistochemistry for TLR4 in bladder cancer specimens. The cancer-specific survival was determined by Kaplan-Meier method and the statistical significance was examined by Log-rank test. We also performed multivariate analysis to evaluate the relationship between TLR4 expression and clinical outcomes. We checked the effects of TLR4 depletion on cell growth and invasive abilities of bladder cancer cells. To clarify the underlying mechanisms, we also analyzed the gene expression profiles in TLR4-depleted cells. These results were validated by quantitative RT-PCR. We also confirmed our finding by using data from public database. RESULTS The expression levels of TLR4 were inversely correlated with local invasion and worse prognosis (log-rank test, p=0.007). Although the effect of TLR4 depletion on cell growth was small, it could dramatically enhance invasion ability of cancer cells. We also observed morphologic changes in these cells. Both gene ontology analysis and gene set enrichment analysis of microarray data revealed that most of upregulated genes in TLR4-depleated cells were related to differentiation of epithelium cells. Among these genes, small proline-rich protein (SPRR) family genes which are related to poor prognosis of squamous cell carcinoma were upregulated in TLR4-depleated cells. By analyzing data from public database, we confirmed that expression levels of SPRRs family genes were inversely correlated with TLR4 expression and positively correlated with poor prognosis of bladder cancer patients. Furthermore, we found that expression of TLR4 diminished in the areas with squamous differentiation in bladder cancer. CONCLUSIONS Our finding suggested that TLR4 is related to bladder cancer aggressiveness through regulation of squamous differentiation. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1319 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Tomoya Fukawa More articles by this author Terumichi Shintani More articles by this author Kei Daizumoto More articles by this author Tomoharu Fukumori More articles by this author Masayuki Takahashi More articles by this author Hiro-omi Kanayama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Knocking down glycoprotein nonmetastatic melanoma protein B suppresses the proliferation, migration, and invasion in bladder cancer cells.

Glycoprotein nonmetastatic melanoma protein B is a type 1 transmembrane protein that has been recently found to play a role in cancer cell proliferation, angiogenesis, and invasion. Due to its potential responsibility in cancer aggressiveness, the main objective of this work was to investigate its expression in bladder cancer and the biological functions in bladder cancer cells. Using immunohistochemistry, western blot, and reverse transcription polymerase chain reaction, we analyzed the expression of glycoprotein nonmetastatic melanoma protein B in bladder cancer tissues and bladder cancer cell lines. The effects of glycoprotein nonmetastatic melanoma protein B on proliferation, migration, and invasion were tested after knocking down the glycoprotein nonmetastatic melanoma protein B in bladder cancer cells with small interfering RNAs by CCK-8, Transwell, and Matrigel assays. Our results showed that glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer tissues and cell lines. Downregulating glycoprotein nonmetastatic melanoma protein B could suppress the proliferation, migration, and invasion in bladder cancer cells. Glycoprotein nonmetastatic melanoma protein B expression was related to the poor differentiation and recurrence by immunohistochemistry analysis. The survival analysis also showed that glycoprotein nonmetastatic melanoma protein B was related to the patient prognosis. In conclusion, Glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer, which was related to the poor prognosis in bladder cancer patients. Glycoprotein nonmetastatic melanoma protein B promoted the proliferation, migration, and invasion in bladder cancer cells.

Assessment of p53 mutations, expression and prognosis in bladder cancer patients from Jordan: Identification of novel deletion mutations in the DNA-binding domain

Bladder cancer is the most common cancer of the urinary tract with an estimate of 401,000 new cases diagnosed annually worldwide. In Jordan, bladder cancer accounts for 4.3% of all newly diagnosed cancer cases. Several studies have linked p53 molecular changes to tumor initiation, invasion, metastasis, and chemoresistance. In the present study, we investigated a cohort of 121 bladder cancer patients with various grades and stages of the tumor for molecular changes in p53. Overexpression of p53 was shown in 22%, 46%, 71% and 25% pTa, pT1, pT2 and pT4 cases, respectively. Additionally, p53 was overexpressed in 19%, 38% and 74% of G1, G2 and G3 cases of bladder cancer, respectively. p53 expression is not significantly associated with the stage or grade of the disease. Mutational analysis of exons 4–8 of p53 identified the following previously reported point mutations R72P (58%), P67T (9%), A159P (0.7%), D185N (28%), G199V (0.7%), G199E (0.7%), D208N (0.7%), R283P (1.4%). Furthermore, we were able to identify two new deletion mutations located in the DNA-binding domain in two patients. The first mutation was a result of one nucleotide deletion in exon 5 causing a frameshift at codon 115 resulting in a truncated 168 amino acids long p53 protein and the second is a result of a whole codon deletion in exon 6 resulting in a p53 protein missing a valine residue at codon 218. P53 mutations were found to be significantly associated with late stage (pT2-pT4) muscle-invasive bladder tumors. Survival analysis indicates significant differences of overall survival between the patients with the p53 overexpression and those with negative p53 staining (p=0.0041). Additionally, were able to observe a significant difference of overall survival between p53 mutants and p53 wild-type (p=0.0062). The present work points to the variable spectrum of TP53 mutations and p53 expression profile in Jordanian patients with bladder cancer and reflects the importance of p53 alterations in predicting poor prognosis of bladder cancer patients.

Overexpression of ribonucleotide reductase subunit M1 protein predicts shorter survival in metastatic bladder cancer patients treated with gemcitabine-containing combination chemotherapy.

To identify biomarkers predicting prognosis in bladder cancer patients undergoing the gemcitabine and cisplatin regimen. We studied 52 patients with metastatic bladder cancer treated with the gemcitabine and cisplatin regimen by evaluating the relationship between the expression of two biomarkers, ribonucleotide reductase subunit M1 and excision repair cross complementing 1, by immunohistochemistry and clinical outcomes. The patients with low expression of ribonucleotide reductase subunit M1 showed a higher objective response rate by the gemcitabine and cisplatin regimen than those with high expression of ribonucleotide reductase subunit M1 (80.0% and 45.5%, respectively). No differences were observed according to the expression level of excision repair cross complementing 1. Low expression of ribonucleotide reductase subunit M1 significantly prolonged overall survival and progression-free survival compared with the high expression group. Low expression of excision repair cross complementing 1 tended to prolong overall survival and progression-free survival, but there were no significant differences (P = 0.07 and 0.10, respectively). Multivariate analysis showed that the expression of ribonucleotide reductase subunit M1 was the only independent prognostic factor (P = 0.012). The expressions of ribonucleotide reductase subunit M1 seem to be associated with clinical response and survival in patients with metastatic bladder cancer treated with gemcitabine and cisplatin-based chemotherapy.

Can the Preoperative Neutrophil-to-Lymphocyte Ratio Significantly Predict the Conditional Survival Probability in Muscle-invasive Bladder Cancer Patients Undergoing Radical Cystectomy?

The present study investigated the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in bladder cancer patients undergoing radical cystectomy (RC), with a focus on the conditional survival (CS) estimates over time after surgery. We analyzed 385 bladder cancer patients who underwent RC from 1999 to 2012. The patients were classified into 2 groups according to the preoperative NLR (< 2.5 vs.≥ 2.5). The Kaplan-Meier survival analysis was used to calculate the conditional probabilities of cancer-specific survival and overall survival after surgery. Multivariate Cox regression models were used to identify the predictors of 5-year conditional cancer-specific survival and overall survival. Patients with an elevated preoperative NLR (≥2.5) had a greater proportion of advanced-stage tumors (≥ pT3), high-grade tumors, and lymphovascular invasion. Patients with an elevated preoperative NLR (≥ 2.5) had poor CS estimates compared with those with a lower NLR (<2.5) at baseline and 1 year after RC. However, no significant differences in CS probabilities were observed from 2 years after RC onward. In a multivariate Cox regression analysis, the preoperative NLR was identified as a significant predictive factor for 5-year CS at baseline and postoperative 1-year estimation; however, its significance was lost after 2 years postoperatively. Our study results suggest that the dynamic aspect of the NLR should be considered when assessing the prognosis of bladder cancer patients treated with RC over time after the initial estimates, in particular, in patients who have already survived for additional years after surgery.

Tetracycline-controllable artificial microRNA-HOTAIR + EZH2 suppressed the progression of bladder cancer cells.

Previous studies have suggested that EZH2 is up-regulated in bladder cancer tissues and identified it as a biomarker for poor prognosis. However, the biological functions of EZH2 in bladder cancer cells remain unknown. In this research, we discovered that EZH2 expression is irrelevant to the TNM stage and poor prognosis of bladder cancer patients. But suppression of EZH2 can slowdown the progression of bladder cancer cells. Moreover, we used the technology of synthetic biology to construct the tetracycline-controllable artificial microRNA-HOTAIR + EZH2, which can decrease the expression of HOTAIR and EZH2 in a doxycycline dosage-dependent manner. And we also found that HOTAIR expression was positively correlated with EZH2 expression. Tetracycline-controllable artificial microRNA-HOTAIR + EZH2 can inhibit the proliferation and migration of bladder cancer cells. Meanwhile, the apoptosis rate of bladder cancer cells was increased. Taken together, our research showed the cancer-promoting effects of EZH2 and created a novel method to rescue the development of bladder cancer cells.

Overexpression of PTK6 predicts poor prognosis in bladder cancer patients.

Protein tyrosine kinase 6 (PTK6) is a non-receptor tyrosine kinase and works as an oncogene in various cancers. Recently, PTK6 has been used as a therapeutic target for breast cancer patients in a clinical study. However, the prognostic value of PTK6 in bladder cancer (BC) remains vague. Therefore, we retrieved 3 independent investigations of Oncomine database and found that PTK6 is highly expressed in BC tissues compared with corresponding normal controls. Similar results were also observed in clinical specimens at both mRNA and protein levels. Immunohistochemical analysis indicated that PTK6 overexpression was highly related to the T classification, N classification, grade, recurrence, and poor prognosis of BC patients. Furthermore, we demonstrated that when PTK6 expression was knocked down by siRNAs, cell proliferation and migration were considerably inhibited in BC cell lines T24 and EJ. By these approaches, we are intended to elucidate PTK6 may be a reliable therapeutic target in BC and might benefit from PTK6 inhibitors in the future.

High expression of B23 is associated with tumorigenesis and poor prognosis in bladder urothelial carcinoma.

B23, a multifunctional nucleolar protein, is overexpressed in numerous cancers and is associated with tumorigenesis. However, the clinical significance and potential role of B23 in bladder urothelial carcinoma remains to be elucidated. The present study observed that the mRNA and protein expression levels of B23 were increased in bladder cancer cells and tissues. The overexpression of B23 contributed to tumorigenesis and was associated with poor prognosis in bladder cancer patients. Silencing of B23 by short hairpin RNA inhibited tumor cell growth and colony formation. In addition, knockdown of B23 suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), resulting in the inactivation of the ERK signaling pathway. Therefore, the present study indicated that B23 promotes bladder cancer cell growth via activation of the ERK signaling pathway and is a novel potential biomarker for the diagnosis and prognosis of bladder cancer.

Clinicopathological and Prognostic Value of Ki-67 Expression in Bladder Cancer: A Systematic Review and Meta-Analysis

BackgroundKi-67 is an established marker of cell proliferation, and the Ki-67 index correlates with the clinical course of several cancer types, including bladder cancer (BC). However, the clinicopathological and prognostic significance of Ki-67 in bladder cancer remains unclear. Therefore, we performed a systematic review and meta-analysis to clarify this relationship.MethodsA comprehensive literature search for relevant studies published up to February 1, 2016, was performed using PubMed, Cochrane Library, Embase and ISI Web of Knowledge. The effects of Ki-67 expression on survival outcome in patients with BC and BC subtypes were evaluated. Furthermore, the relationship between Ki-67 expression and the clinicopathological features of BC were assessed.ResultsThirty-one studies with 5147 bladder cancer patients were selected for evaluation. Ki-67 expression was significantly associated with shorter recurrence-free (HR 1.69, 95% CI: 1.33–2.14), progression-free (HR 1.89, 95% CI: 1.43–2.51), overall (HR 2.03, 95% CI: 1.31–3.16), and cancer-specific (HR 1.69, 95% CI: 1.47–1.95) survival. Moreover, whereas high expression was more common in high tumor stage, recurrence status, tumor size, there was no correlation between high Ki-67 expression and age, gender, smoking habits, and tumor number. Importantly, analysis of the different subgroups of BC suggested that significant correlations between high Ki-67 expression and survival outcome (recurrence-free/progression-free/overall/cancer-specific survival) are present only in European-American patients.ConclusionThe present results indicate that over-expression of Ki-67 is distinctly correlated with poor patient survival. Ki-67 may serve as a valuable biomarker for prognosis in BC patients, particularly in non-Asian BC patients. The results suggest no significant association between Ki-67 expression and BC prognosis in Asian patients. Further efforts are needed to fully clarify this relationship.

Impact of photodynamic diagnosis-assisted transurethral resection of bladder tumors on the prognostic outcome after radical cystectomy: results from PROMETRICS 2011.

Results of a retrospective single-institution study recently suggested improved prognostic outcomes in patients undergoing photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) prior to radical cystectomy (RC). We sought to validate the prognostic influence of PDD-assisted TURBT on survival after RC by relying on a multi-institutional dataset. To provide a homogeneous study population, patients with organ metastasis at the time of RC and/or after neoadjuvant chemotherapy were excluded from analysis, which resulted in overall 549 bladder cancer (BC) patients from 18 centers of the Prospective Multicenter Radical Cystectomy Series 2011 (PROMETRICS 2011). To evaluate the influence of PDD conducted during primary or final TURBT on cancer-specific mortality (CSM) and overall mortality (OM) after RC, bootstrap-corrected multivariate Cox proportional-hazards regression models were applied (median follow-up: 25months; IQR: 19-30). Sensitivity analyses were performed for both patients with pure urothelial carcinoma and patients undergoing one single TURBT only. In 88 (16.0%) and 100 (18.2%) patients, PDD was used in primary and final TURBTs, respectively. In 335 (61.0%) patients, a single TURBT was performed prior to RC; in 194 patients (35.3%), TURBT had been performed in a different center. CSM and OM rates at 3years were 32 and 40%, respectively. Use of PDD during primary or final TURBT was no independent predictor of CSM or OM. These results were internally valid and were confirmed in sensitivity analyses. PDD utilization during TURBT prior to RC does not independently impact the prognosis of BC patients after RC.

Can we use methylation markers as diagnostic and prognostic indicators for bladder cancer?

Urothelial carcinomas of the urinary bladder have diverse biological and functional characteristics, and numerous factors are likely to be involved in recurrence, progression, and patient survival. While several molecular markers used to evaluate the development and prognosis of bladder cancer have been studied, they are of limited value; therefore, new molecular parameters useful for predicting the prognosis of bladder cancer patients (particularly patients at high risk of progression and recurrence) are required. Recent progress in the understanding of epigenetic modification and gene silencing has provided new opportunities for the detection, treatment, and prevention of cancer. Methylation is an important molecular mechanism in bladder cancer and may have utility as a prognostic and/or diagnostic marker. This review discusses the epigenetic issues involved in the detection and prediction of bladder cancer.

Association of thymosin β4 expression with clinicopathological parameters and clinical outcomes of bladder cancer patients.

The clinical significance of thymosin β4 (Tβ4) expression in bladder transitional cell carcinoma (BTCC) remains unclear. The present study assessed the relationship between the expression of Tβ4 protein and the clinicopathological features, as well as the prognosis of bladder cancer patients. Tβ4 protein expression in 24 normal bladder and 138 primary BTCC tissue specimens was detected by immunohistochemistry, and the association of this expression with BTCC clinicopathological features and recurrence as well as patient survival was analyzed. Tβ4 expression was significantly stronger in BTCC patients than in normal volunteers. The expression of Tβ4 was significantly associated with differentiation capability, tumor stage and lymph node metastasis (P = 0.025, 0.043, and 0.039, respectively). Moreover, Tβ4 expression was positively correlated with integrin-linked kinase (ILK) and β-catenin expression (P = 0.042, 0.031, respectively) and inversely correlated with E-cadherin expression (P = 0.022). In the present cohort of bladder cancer patients, Tβ4 expression was found to be a predictor of poor survival (P < 0.05); however, high Tβ4 expression exhibited unfavorable prognostic value for recurrence. These data suggested that Tβ4 is correlated with the pathogenesis of BTCC. In addition, the patients with higher Tβ4 expression had a shorter survival.

MicroRNA-148a represents an independent prognostic marker in bladder cancer.

A previous study has demonstrated the roles of microRNA-148a (miR-148a) on apoptosis of bladder cancer cells. The goal of this study was to investigate whether the miR-148a expression level could serve as a new biomarker for the prognosis of bladder cancer patients. We collected a total of 126 bladder cancer samples. The expression level of miR-148a was determined with quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier method was used to analyze the overall survival. Cox regression analysis was further used to identify prognostic factors. The expression levels of miR-148a in bladder cancer tissues were identified (1.5 ± 0.3; P < 0.001). The bladder cancer patients in the low-expression group more frequently had a high tumor grade (P = 0.025), increased tumor recurrence (P = 0.002), and advanced lymph node (LN) metastasis (P = 0.001). Patient survival analysis revealed a clear positive correlation between miR-148a expression level and survival time of bladder cancer patients (P = 0.005, log-rank = 7.714). In univariate Cox proportional hazards regression analysis, we found that a low-expression level of miR-148a (P = 0.018), tumor grade (P = 0.006), lymph node metastasis (P = 0.001), and recurrence (P < 0.001) were associated with the prognosis of bladder cancer. In multivariate analysis, we found that miR-148a expression (RR = 0.206, 95% CI 0.095-0.813, P = 0.029), tumor grade (RR = 0.714, 95% CI 0.224-0.958, P = 0.714), lymph node metastasis (RR = 6.604, 95% CI 3.192-12.547, P < 0.001), and recurrence (RR = 15.126, 95% CI 6.714-22.025, P < 0.001) retained significance as an independent prognostic factor of bladder cancer survival (Table 3). All results have showed that miR-148a expression was decreased in bladder cancer specimens and reduced miR-148a expression was associated with poorer survival time, indicating that miR-148a may become a candidate factor for predicting the prognosis of bladder cancer.