Grade Bladder Cancer Research Articles

The Prevalence and Impact of Urinary Marker Testing in Patients with Bladder Cancer.

Novel urinary tumor markers for bladder cancer may permit early detection and improved oncologic outcomes but data on use is limited. We sought to identify trends in the application of urinary markers and long-term outcomes of urinary tumor marker use in patients with bladder cancer. Data from the SEER (Surveillance, Epidemiology and End Results)-Medicare database from 2001 to 2011 were used to identify a cohort of 64,450 patients with bladder cancer who underwent urinary marker testing with UroVysion® fluorescence in situ hybridization, or the NMP22® or BTA Stat® test. We assessed the prevalence of urinary marker testing and urine cytology. Characteristics of patients who did and did not undergo urinary marker testing were analyzed by the chi-square test. Urinary marker testing predictors were analyzed with a multivariable logistic regression model and Cox proportional hazards were used to determine unadjusted cancer specific and overall mortality risks. The rate of urinary marker testing increased from 17.8% to a peak of 28.2% during the study years (p <0.0001). Predictors of marker use included female gender, younger age and lower Charlson score. Overall and cancer specific survival improved on Kaplan-Meier and Cox proportional hazards analyses with urinary marker testing. Increased urinary marker testing was documented over all stages and grades of bladder cancer, and in certain patient and provider variables. This increase may have contributed to improved overall and cancer specific survival. Additional investigation is necessary to further characterize this benefit.

CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells.

Increasing evidences suggest that circular RNAs (circRNAs) exert crucial functions in regulating gene expression. In this study, we perform RNA-seq and identify 6,154 distinct circRNAs from human bladder cancer and normal bladder tissues. We find that hundreds of circRNAs are significantly dysregulated in human bladder cancer tissues. We further show that circHIPK3, also named bladder cancer-related circular RNA-2 (BCRC-2), is significantly down-regulated in bladder cancer tissues and cell lines, and negatively correlates with bladder cancer grade, invasion as well as lymph node metastasis, respectively. Over-expression of circHIPK3 effectively inhibits migration, invasion, and angiogenesis of bladder cancer cells invitro and suppresses bladder cancer growth and metastasis invivo Mechanistic studies reveal that circHIPK3 contains two critical binding sites for the microRNA miR-558 and can abundantly sponge miR-558 to suppress the expression of heparanase (HPSE). Taken together, our findings provide evidence that circRNAs act as "microRNA sponges", and suggest a new therapeutic target for the treatment of bladder cancer.

UBC®RapidTest for detection of carcinoma in situ for bladder cancer

UBC® Rapid Test is a test that detects fragments of cytokeratins 8 and 18 in urine. We present results of a multicentre study measuring UBC® Rapid Test in bladder cancer patients and healthy controls with focus on carcinoma in situ (CIS) and high-grade bladder cancer. From our study with N = 452 patients, we made a stratified sub-analysis for carcinoma in situ of the urinary bladder. Clinical urine samples were used from 87 patients with tumours of the urinary bladder (23 carcinoma in situ, 23 non-muscle-invasive low-grade tumours, 21 non-muscle-invasive high-grade tumours and 20 muscle-invasive high-grade tumours) and from 22 healthy controls. The cut-off value was defined at 10.0 µg/L. Urine samples were analysed by the UBC® Rapid Test point-of-care system (concile Omega 100 POC reader). Pathological levels of UBC Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p < 0.001). Sensitivity was calculated at 86.9% for carcinoma in situ, 30.4% for non-muscle-invasive low-grade bladder cancer, 71.4% for nonmuscle-invasive high grade bladder cancer and 60% for muscle-invasive high-grade bladder cancer, and specificity was 90.9%. The area under the curve of the quantitative UBC® Rapid Test using the optimal threshold obtained by receiveroperated curve analysis was 0.75. Pathological values of UBC® Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumours and the healthy control group. UBC® Rapid Test has potential to be more sensitive and specific urinary protein biomarker for accurate detection of high-grade patients and could be added especially in the diagnostics for carcinoma in situ and non-muscle-invasive high-grade tumours of urinary bladder cancer.

Effects of increased Kindlin-2 expression in bladder cancer stromal fibroblasts.

Kindlin-2 is a focal adhesion protein highly expressed in bladder cancer stromal fibroblasts. We investigated the prognostic significance of Kindlin-2 in bladder cancer stromal fibroblasts and evaluated the effects of Kindlin-2 on the malignant behaviors of tumor cells. Immunohistochemical staining of 203 paraffin-embedded bladder cancer tissues showed that Kindlin-2 expression correlated with advanced stage, high grade, and relapse of bladder cancer. Kaplan-Meier survival analysis demonstrated that patients exhibiting high Kindlin-2 expression had shorter survival times than those with low Kindlin-2 expression (p < 0.01). Multivariate analysis revealed that high Kindlin-2 expression leads to poor prognosis in bladder cancer. Using cancer-associated fibroblasts (CAFs) isolated from human bladder cancer tissue, we observed that Kindlin-2 knockdown decreased CAFs activation, resulting in decreased expression of α-smooth muscle actin (α-SMA) and the extracellular matrix protein fibronectin. Kindlin-2 suppression also reduced CAF-induced bladder cancer cell migration and invasion. Moreover, we found that Kindlin-2 activates CAFs and promotes the invasiveness of bladder cancer cells by stimulating TGF-β-induced epithelial-mesenchymal transition. These results support targeting Kindlin-2 and the corresponding activated CAFs in bladder cancer therapy.

Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

To address the shortcomings of cystoscopy and urine cytology for detecting and grading bladder cancer (BC), ultrahigh performance liquid chromatography (UHPLC) coupled with Q-TOF mass spectrometry in conjunction with univariate and multivariate statistical analyses was employed as an alternative method for the diagnosis of BC. A series of differential serum metabolites were further identified for low-grade(LG) and high-grade(HG) BC patients, suggesting metabolic dysfunction in malignant proliferation, immune escape, differentiation, apoptosis and invasion of cancer cells in BC patients. In total, three serum metabolites including inosine, acetyl-N-formyl-5-methoxykynurenamine and PS(O-18:0/0:0) were selected by binary logistic regression analysis, and receiver operating characteristic (ROC) test based on their combined use for HG BC showed that the area under the curve (AUC) was 0.961 in the discovery set and 0.950 in the validation set when compared to LG BC. Likewise, this composite biomarker panel can also differentiate LG BC from healthy controls with the AUC of 0.993 and 0.991 in the discovery and validation set, respectively. This finding suggested that this composite serum metabolite signature was a promising and less invasive classifier for probing and grading BC, which deserved to be further investigated in larger samples.

Prognostic Value of p53 Expression Intensity in Urothelial Cancers.

To determine association of immunohistochemical expression intensity of p53 with grade and stage of urothelial cancers. Descriptive cross-sectional analytical study. Pathology Department, King Edward Medical University, Lahore, from January to December 2016. Data of transurethral resection/radical cystesctomy urinary bladder biopsies was collected. Clinical, radiological and cystoscopic findings of patients were noted from patients' charts in the Urology Ward. Biopsies were graded histologically according to WHO 2004 grading system. TNM system was used for pathological staging. On selected slides, immunoshistochemistry for p53 was applied. Nuclear immunoreactivity was considered positive if present in >10% of tumor cells and negative if <10% of tumor cells. Intensity was considered weak (less than 15% cells) and strong (more than 15% cells). Data was analyzed by SPSS version 21. Linear-by-linear association was calculated between p53 expression and stage of urothelial tumors, Chi-Square test was used to see association between grade and intensity of p53. Qualitative variables, like grade and stage of carcinoma along with p53 expression, were calculated in terms of frequencies and percentages. P ≤ 0.05 was taken as significant. Out of the 70 patients, 61 (87%) were males and 9 (13%) females. Out of 25 low grade lesions, 4 (16%) cases were p53 positive; and out of 45 high grade lesions, 41 (91%) cases were p53 positive. There was 33% (2/6 cases) positivity in Tis, 55% (16/29 cases) in T1, 72% in T2 (21/29), and 100% in T3a (5/5 cases) and T3b (1/1 case). Strong intensity of p53 staining was noted to be 5.4% (n=25) of low grade and 94.6% (n=45) of high grade tumors. p53 expression was greater and more frequently strong in higher grade and stage of urothelial carcinoma. It can be used as a prognostic marker in predicting higher grade and stage of bladder cancer.

MP04-18 SMOKING INTENSITY AS A PREDICTOR OF SURVIVAL IN BLADDER CANCER PATIENTS: RESULTS FROM A POPULATION-BASED FLORIDA CANCER REGISTRY (1981-2009)

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I1 Apr 2017MP04-18 SMOKING INTENSITY AS A PREDICTOR OF SURVIVAL IN BLADDER CANCER PATIENTS: RESULTS FROM A POPULATION-BASED FLORIDA CANCER REGISTRY (1981-2009) Luís Felipe Sávio, Tulay Koru-Sengul, Diana M Lopategui, Feng Miao, Nachiketh Soodana Prakash, Bruno Nahar, Vivek Venkatramani, Sanjaya Swain, Sanoj Punnen, Dipen J Parekh, Chad Ritch, and Mark L. Gonzalgo Luís Felipe SávioLuís Felipe Sávio More articles by this author , Tulay Koru-SengulTulay Koru-Sengul More articles by this author , Diana M LopateguiDiana M Lopategui More articles by this author , Feng MiaoFeng Miao More articles by this author , Nachiketh Soodana PrakashNachiketh Soodana Prakash More articles by this author , Bruno NaharBruno Nahar More articles by this author , Vivek VenkatramaniVivek Venkatramani More articles by this author , Sanjaya SwainSanjaya Swain More articles by this author , Sanoj PunnenSanoj Punnen More articles by this author , Dipen J ParekhDipen J Parekh More articles by this author , Chad RitchChad Ritch More articles by this author , and Mark L. GonzalgoMark L. Gonzalgo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.156AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There is limited information regarding the association between smoking intensity and survival trends among patients with bladder cancer (BC). We examined demographic and survival trends for patients diagnosed with BC stratified by smoking intensity. METHODS The Florida Cancer Data System (FCDS) linked with US census data was used to identify all smoking adult patients =18 years residing in Florida diagnosed with BC between 1981 and 2009. Median and 5-year overall survival rates were compared between patients that smoked <1, 1-2, and >2 packs of cigarettes per day (PPD). A multivariable Cox regression model was used to determine the adjusted hazard ratio (AHR) along with 95% confidence interval (95% CI) for mortality after adjustment for age at diagnosis, sex, race, ethnicity, socioeconomic status (SES), marital status, regional lymph node positvity, treatment, grade, and stage of BC. RESULTS Of the 14,077 smoking BC patients, 25%, 63%, and 12% smoked <1, 1-2, and >2 PPD, respectively. The majority of patients were males (74%), Whites (96%), living in an urban area (94%), and with a middle-high/highest SES (53%). The majority of them had localized BC (73%). Median overall survival and 5-year survival rates for the entire cohort were 4.0 years and 43.7% (95%CI: 42.7-44.7), respectively. Median overall survival for patients smoking <1, 1-2, and >2 PPD was 4.2 years, 3.9 years, and 4.1 years, respectively. The 5-year survival rates for patients smoking <1, 1-2, and >2 PPD were 45.1% (43.1-47.1), 43.1% (41.8-44.3), and 43.6% (40.9-46.3), respectively. Patients smoking 1-2 PPD ([HR] 1.11; 95% CI 1.06-1.16, p<0.001) and >2 PPD ([1.08] 1.00-1.16, p=0.042] were significantly more likely to have a higher risk of mortality compared to patients that smoked <1 PPD on multivariate analysis. CONCLUSIONS Higher smoking intensity is associated with an increased risk of mortality among patients with BC. These data highlight the importance of smoking cessation for BC patients and underscore the need for patient education regarding the dangers of smoking. Smoking cessation efforts should be targeted to this population since even a small reduction in the amount of smoking may still have potential survival benefit. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e35 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Luís Felipe Sávio More articles by this author Tulay Koru-Sengul More articles by this author Diana M Lopategui More articles by this author Feng Miao More articles by this author Nachiketh Soodana Prakash More articles by this author Bruno Nahar More articles by this author Vivek Venkatramani More articles by this author Sanjaya Swain More articles by this author Sanoj Punnen More articles by this author Dipen J Parekh More articles by this author Chad Ritch More articles by this author Mark L. Gonzalgo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP88-04 THE ADAPTOR PROTEIN CRK-INDUCED ERBB2 EXPRESSION PROMOTES TUMOR PROGRESSION AND METASTASIS OF BLADDER CANCER VIA EXOSOMES

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV1 Apr 2017MP88-04 THE ADAPTOR PROTEIN CRK-INDUCED ERBB2 EXPRESSION PROMOTES TUMOR PROGRESSION AND METASTASIS OF BLADDER CANCER VIA EXOSOMES Kazuhiko Yoshida, Masumi Tsuda, Ryuji Matsumoto, Shingo Semba, Taichi Kimura, Mishie Tanino, Hiroshi Nishihara, Tsunenori Kondo, Kazunari Tanabe, and Shinya Tanaka Kazuhiko YoshidaKazuhiko Yoshida More articles by this author , Masumi TsudaMasumi Tsuda More articles by this author , Ryuji MatsumotoRyuji Matsumoto More articles by this author , Shingo SembaShingo Semba More articles by this author , Taichi KimuraTaichi Kimura More articles by this author , Mishie TaninoMishie Tanino More articles by this author , Hiroshi NishiharaHiroshi Nishihara More articles by this author , Tsunenori KondoTsunenori Kondo More articles by this author , Kazunari TanabeKazunari Tanabe More articles by this author , and Shinya TanakaShinya Tanaka More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2729AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Molecular targeted therapies have been developed for various cancers, however; which have not advanced beyond conventional chemotherapy for the locally advanced and metastatic bladder cancer (BC). Therefore, establishment of more efficient therapeutic strategy is urgently desired. Recently, extracellular exosomes are paid attention as important mediators of intercellular communication. Tumor-derived exosomes have known to transfer proteins and nucleic acids from the cells of origin to target cells and affect tumor progression and metastatic process. We have been reported that signaling adaptor protein CRK promotes cell growth, invasion, and adhesion in various cancers, however; the relationship between CRK and exosomes has remained unknown. Here, we investigated the effects of CRK-mediated exosomes on tumor progression and metastasis of BC. METHODS Human BC cell line UM-UC-3 were stably transfected with pCSII-CMV-tdTomato-Luc, and CRK was knocked-down by shRNA technique. The parental and CRK-depleted cells (CRKi) were orthotopically injected into nude mice, and the tumor progression and metastasis were investigated using IVIS Spectrum. In in vitro setting, expression levels of proteins associated with cell growth, survival, and invasion were examined in parental and CRKi UM-UC-3 cells and their exosomes, and the proteins contained in exosomes were identified by LC-TOF/MS. Low grade BC 5637 cells and HUVECs were treated with exosomes from parental UM-UC-3 cells, and the cell proliferation and invasion were analyzed. Furthermore, the metastases in mice pretreated with exosomes from parental and CRKi cells were investigated. RESULTS CRKi UM-UC-3 cells inhibited the tumor progression and metastasis in orthotopic xenograft models. We found that CRK and ErbB2 were contained in exosome from the parental UM-UC-3 cells, and the exosomes-incorporated-5637 and -HUVECs significantly promote the cell proliferation and invasion. In contrast, in exosomes from CRKi cells, the expression levels of ErbB2 were reduced, and the exosome-incorporated recipient cells decreased the growth and invasion. Of note, lung metastasis of UM-UC-3 cells was facilitated in mice educated by the parental UM-UC-3-derived exosomes, but not by CRKi cells-derived exosomes. CONCLUSIONS Here, we provide novel findings that CRK-regulated up-regulation of ErbB2 in the exosomes of BC facilitated the tumor progression and metastasis. Therefore, CRK and ErbB2 might be potent therapeutic targets to prevent the locally advanced and metastasis for BC patients. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1175 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Kazuhiko Yoshida More articles by this author Masumi Tsuda More articles by this author Ryuji Matsumoto More articles by this author Shingo Semba More articles by this author Taichi Kimura More articles by this author Mishie Tanino More articles by this author Hiroshi Nishihara More articles by this author Tsunenori Kondo More articles by this author Kazunari Tanabe More articles by this author Shinya Tanaka More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Utility of early dynamic and delayed post-diuretic 18F-FDG PET/CT SUVmax in predicting tumour grade and T-stage of urinary bladder carcinoma: results from a prospective single centre study.

Accurate pre-treatment grading and staging of bladder cancer are vital for better therapeutic decision and prognosis. The aim of the present study was to evaluate the correlation between maximum standardized uptake value (SUVmax) calculated during early dynamic and post-diuretic fluorine-18 fludeoxyglucose (18F-FDG) positron emission tomography (PET)/CT studies with grade and pT-stage of bladder cancer. 39 patients with suspected/proven bladder carcinoma underwent 10-min early dynamic pelvic imaging and delayed post-diuretic whole-body FDG PET/CT imaging. SUVmax of the lesions derived from both studies was compared with grade and pT-stage. Relationship of SUVmax with grade and pT-stage was analyzed using independent sample t-test and analysis of variance. SUVmax of the early dynamic imaging showing tumour perfusion was independent from the SUVmax of delayed imaging. High-grade tumours showed higher SUVmax than low-grade tumours in the early dynamic imaging (5.4 ± 1.4 vs 4.7 ± 1.6; p-value 0.144) with statistically significant higher value in Stage pT1 tumours (6.8 ± 0.8 vs 5.5 ± 1.2; p-value 0.04). Non-invasive pTa tumours had significantly less SUVmax than higher stage tumours during early dynamic imaging [F(4,29) = 6.860, p 0.001]. Early dynamic imaging may have a role in predicting the grade and aggressiveness of the bladder tumours and thus can help in treatment planning and prognostication. Advances in knowledge: Dynamic PET/CT is a limitedly explored imaging technique. This prospective pilot study demonstrates the utility of this modality as a potential adjunct to standard FDG PET/CT imaging in predicting the grade and aggressiveness of the bladder tumours and thus can impact the patient management.

128 - Molecular tumour grading and classification of non muscle invasive bladder cancer based on whole transcriptome analysis

128 - Molecular tumour grading and classification of non muscle invasive bladder cancer based on whole transcriptome analysis

Increased expression of ZEB1-AS1 correlates with higher histopathological grade and promotes tumorigenesis in bladder cancer.

Bladder cancer is one of the most common urinary cancers worldwide. Emerging studies indicated that long non-coding RNAs (lncRNAs) play crucial roles in cancer biology. In this study, we found that a novel lncRNA Zinc finger E-box-binding homeebox1 (ZEB1) antisense RNA (ZEB1-AS1) was overexpressed in bladder cancer tissues compared to paired noncancerous tissues. Moreover, the expression of ZEB1-AS1 was positive correlated with higher histological grade and TNM stage in bladder cancer. Furthermore, Loss-of-function experiments showed that down-regulation of ZEB1-AS1 not only can suppress cell growth but also can inhibit migration and induce apoptosis in bladder cancer cell lines 5637 and SW780. In conclusion, these findings indicated that ZEB1-AS1 plays regulatory roles in bladder cancer and it may become a novel molecular biomarker of prognosis and therapy in bladder cancer.

Radiomics assessment of bladder cancer grade using texture features from diffusion-weighted imaging.

To 1) describe textural features from diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps that can distinguish low-grade bladder cancer from high-grade, and 2) propose a radiomics-based strategy for cancer grading using texture features. In all, 61 patients with bladder cancer (29 in high- and 32 in low-grade groups) were enrolled in this retrospective study. Histogram- and gray-level co-occurrence matrix (GLCM)-based radiomics features were extracted from cancerous volumes of interest (VOIs) on DWI and corresponding ADC maps of each patient acquired from 3.0T magnetic resonance imaging (MRI). A Mann-Whitney U-test was applied to select features with significant differences between low- and high-grade groups (P < 0.05). Then support vector machine with recursive feature elimination (SVM-RFE) and classification strategy was adopted to find an optimal feature subset and then to establish a classification model for grading. A total 102 features were derived from each VOI and among them, 47 candidate features were selected, which showed significant intergroup differences (P < 0.05). By the SVM-RFE method, an optimal feature subset including 22 features was further selected from candidate features. The SVM classifier using the optimal feature subset achieved the best performance in bladder cancer grading, with an area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity of 0.861, 82.9%, 78.4%, and 87.1%, respectively. Textural features from DWI and ADC maps can reflect the difference between low- and high-grade bladder cancer, especially those GLCM features from ADC maps. The proposed radiomics strategy using these features, combined with the SVM classifier, may better facilitate image-based bladder cancer grading preoperatively. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1281-1288.

Is Bacillus Calmette-Guerin (BCG) still the best adjuvant treatment after Trans Urethral Resection (TUR) for Ta-T1 high grade (G3) bladder cancer

Is Bacillus Calmette-Guerin (BCG) still the best adjuvant treatment after Trans Urethral Resection (TUR) for Ta-T1 high grade (G3) bladder cancer

275P Clinical outcomes of second transurethral resection in non-muscle invasive high grade bladder cancer: a retrospective, multi-institutional, collaborative study

275P Clinical outcomes of second transurethral resection in non-muscle invasive high grade bladder cancer: a retrospective, multi-institutional, collaborative study

Targeting protein kinase CK2 suppresses bladder cancer cell survival via the glucose metabolic pathway.

Casein kinase 2 (CK2) is a constitutively active serine/threonine kinase that promotes cell proliferation and resists apoptosis. Elevated CK2 expression has been demonstrated in several solid tumors. The expression of CK2α in bladder cancer was elevated in tumor tissues compared with that in adjacent normal tissues. Amplified expression of CK2α was highly correlated with histological grade in bladder cancer(P = 0.024). Knockdown of CK2α in bladder cancer cell lines resulted in a reduction in tumor aerobic glycolysis, accompanied with lower phosphorylated AKT. Moreover, low CK2α levels suppressed cell growth, and similar results could be reproduced after treatment with CX-4945 with a dose-dependent response. CX-4945 inhibited migration and induced apoptosis. Furthermore, knockdown of CK2α decreased the tumorigenicity of bladder cancer cells in vivo. This study is the first to report that CK2 increases glucose metabolism in human bladder cancer. Blocking CK2 function may provide novel diagnostic and potential therapeutic.

Common and differentially expressed long noncoding RNAs for the characterization of high and low grade bladder cancer

Our study aimed to explore long non-coding RNAs (lncRNAs) contributing to the development of bladder cancer, as well as to identify more critical DEGs and lncRNAs that would characterize low- and high-grade bladder cancer. The microarray data of GSE55433 was downloaded from Gene Expression Omnibus database, including 57 urothelial cancer samples (23 low-grade NMI, 14 high-grade NMI and 20 invasive tumors) and 26 normal controls. The differentially expressed genes (DEGs) and differentially expressed lncRNAs were identified in 3 groups (low-grade NMI vs. normal, high-grade NMI vs. normal and invasive UC vs. normal). Functional enrichment analysis was performed upon the DEGs in different groups. Besides, protein-protein interaction (PPI) network was constructed based on common DEGs and remaining DEGs in each group. Co-expression analysis was performed to identify the co-expressed DEG-lncRNAs pairs. Different number of DEGs and differentially expressed lncRNAs were respectively identified from those 3 groups. NONHSAG013805 (down-regulated) and NONHSAG009271 (down-regulated) were common lncRNAs. NONHSAG013805 was connected with the down-regulated gene EIF3E and NONHSAG009271 was linked to MYL12A (down-regulated). Moreover, NONHSAG034203 (up-regulated) was co-expressed with ADM5 (up-regulated) in low-grade NMI cancer, while the down-regulated NONHSAG045391 was connected with the down-regulated DEGs DAD1 and STUB1 in high-grade NMI cancer and invasive bladder cancer. Our study indicates that NONHSAG013805 and NONHSAG009271 may play key roles in bladder cancer via co-expressing with EIF3E and MYL12A, respectively. Moreover, NONHSAG034203 may be involved in low-grade NMI bladder cancer via targeting ADM5, while NONHSAG045391 may contribute to high-grade NMI and invasive bladder cancer via targeting DAD1 and STUB1.

A Functional rs353293 Polymorphism in the Promoter of miR-143/145 Is Associated with a Reduced Risk of Bladder Cancer.

Background and ObjectivesMicroRNA (miR)-143/145, known as tumor suppressors, can promote cell apoptosis and differentiation, and suppress cell proliferation, invasion and migration. We performed a case-control study to investigate the association of rs353293 in the promoter region of miR-143/145 with bladder cancer risk.MethodsIn total, 869 subjects including 333 cases and 536 controls were enrolled in this study, and the rs353293 polymorphism was genotyped by using a Taqman assay. The promoter activity was measured by the Dual-Luciferase Assay System.ResultsWe calculated an adjusted odds ratio of 0.64 for the presence of either AA/AG genotypes (95% CI 0.46–0.90) and 0.64 (95% CI 0.47–0.87) for carrying at least one A allele in bladder cancer. Stratified analyses showed that the AA/AG genotypes and the A allele were less prevalent in patients with low grade tumors, compared to those harboring higher grade bladder cancers (adjusted OR = 0.53, 95% CI, 0.30–0.94, P = 0.03 and adjusted OR = 0.54, 95% CI, 0.32–0.92, P = 0.02, respectively). In vitro luciferase reporter analysis showed that rs353293A allele had a lower activity compared with the rs353293G allele (P < 0.001).ConclusionThese findings suggest that the functional rs353293 polymorphism may be a useful biomarker to predict the risk of bladder cancer.

Abstract 698: Progranulin targeting in urothelial cancer cells inhibits motility, tumor growth in vitro and in vivo and sensitizes cells to cisplatin

Abstract Introduction and Objective: Bladder cancer is a major public health problem and affects more than 74,000 Americans with more than 16,000 estimated deaths in 2015. The majority of deaths are due to metastatic spread, commonly to the lungs. Understanding the molecular mechanisms regulating bladder tumor cell invasion and progression toward metastases is essential for developing better therapies to treat bladder cancer patients. The growth factor progranulin has emerged in recent years as an important regulator of transformation in several cancer models. We have previously established a critical role for progranulin in bladder cancer as in fact progranulin acts as an autocrine growth factor and promote motility and invasion of invasive urothelial cancer cells. In addition, progranulin is upregulated in high grade bladder cancer tissues compared to normal tissue controls suggesting that progranulin might work as a novel biomarker with predictive value for bladder cancer progression. However, whether progranulin is important for anchorage-independent growth and in vivo tumor formation of urothelial cancer cells has not been previously established. Methods: Progranulin depletion was achieved by stably transfecting tumorigenic T24T, UMUC3 urothelial cancer cells with a plasmid expressing an anti-progranulin shRNA. Progranulin-depleted and control UMUC-3 and T24T cells were tested for motility, invasion and anchorage-independent growth by soft-agar assays. Tumor formation in vivo was assessed in various UMUC-3-derived cell lines by xenograft and orthotopic models. Sensitivity to cisplatin was assessed by cell survival curves. Progranulin expression levels in a bladder tissue microarray were analyzed by HIC. Results: Progranulin-depleted T24T and UMUC-3 cells were significantly inhibited in their ability to migrate, close a wound and invade through Matrigel compared to control cells in both serum-deprived and 1% serum media. In addition, progranulin targeting strongly reduced the ability of T24T and UMUC-3 cells to grow in anchorage-independency and form colonies in soft-agar. Significantly progranulin-depleted UMUC-3 cells were severely inhibited in tumor formation in vivo as assessed by both xenograft and orthotopic models in immunocompromised mice. Importantly, progranulin depletion sensitized UMUC-3 cells to cisplatin. Finally, progranulin levels correlated with tumor progression in bladder cancer tissues. Conclusions: Our data are translationally relevant as indicate that progranulin exerts an essential functional role in the regulation of bladder cancer progression. Thus, progranulin may constitute a novel target for therapeutic intervention in bladder tumors. In addition, progranulin may serve as novel biomarker for diagnosis and prognosis of bladder cancer. Citation Format: Simone Buraschi, Shi-Qiong Xu, Manuela Stefanello, Igor Moskalev, Alaide Morcavallo, Marco Genua, Ryuta Tanimoto, Thomas Neill, Stephen C. Peiper, Leonard G. Gomella, Antonino Belfiore, Peter C. Black, Renato V. Iozzo, Andrea Morrione. Progranulin targeting in urothelial cancer cells inhibits motility, tumor growth in vitro and in vivo and sensitizes cells to cisplatin. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 698.

Association between the metabolic syndrome and T1 high grade urothelial carcinoma of the bladder

Objective To summarize the relationship between metabolic syndrome(MS), its components and T1 stage with high grade urothelial carcinoma (HGUC) of the Bladder. Methods The clinical data of 200 patients with T1 high grade bladder cancer who were admitted to our hospital from January 2010 to June 2014 were retrospectively analyzed, including 155 males and 45 females. Ages were 24 to 86 years old, average 66 years old. Based on the history or blood glucose levels, patients were divided into diabetic group (n = 41) (20.5%) and non diabetes group 159 cases (79.5%); According to the body mass index (BMI) were divided into obese group (≥25 kg / m2) of 98 cases (49.0%) and non obese group (< 25 kg / m2) of 102 cases (51.0%). According to the blood pressure level, 71 cases (35.5%) were divided into hypertension group and 129 cases of non hypertension group (64.5%). MS and its components and the relationship between the recurrence and progress of bladder cancer were analyzed. The Kaplan Meier method was used to assess MS and its components division of tumor progression free survival (progress-free survival, PFS) and recurrence free survival (recurrence-free survival, RFS) influence. Cox regression model of multi factor analysis were used to evaluate the PFS and RFs of MS and its components with bladder cancer. Results Of the 200 cases, 16 cases (8.0%) were MS. Tumor recurrence occurred in 121 cases (60.5%), and 84 patients (42.0%) were in progress. Diabetes and non diabetes groups the average RFs were 21.7 and 29.3 months respectively, and the difference was statistically significant (χ2=10.115, P=0.001); The median PFS were 32.8 and 39.8 months respectively, the difference has statistical significance (χ2=14.760, P<0.001). Obese group and non obese group average RFs were 34.7 and 42.0 months respectively, and the difference were statistically significant (χ2=16.077, P<0.001); The median PFS were 22.8 and 32.6 months respectively, the difference was statistically significant (χ2=16.174, P<0.001). The average RFS of MS group and non MS group were 21.5 and 28.4 months respectively, the difference was statistically significant (χ2=5.429, P=0.02); the average PFS was 35.1 and 38.7 months respectively, and the difference was statistically significant (χ2=3.854, P<0.05). Cox multivariate survival analysis showed that diabetes and obesity can increase the risk of recurrence and progression of T1 advanced stage bladder cancer (HR=1.792, P=0.013, HR=2.498, P<0.001; HR=0.559, P<0.001; HR=0.492, P<0.001). Conclusions Diabetes mellitus and obesity are high risk factors for the recurrence and progression of T1 advanced stage bladder cancer, but MS is not related to the prognosis of T1 patients with advanced bladder cancer. Key words: Metabolic syndrome; Urothelial carcinoma; Diabetes mellitus; Hypertension; Obesity

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.