Survival In Bladder Cancer Patients Research Articles

Bone Metastases Pattern in Newly Diagnosed Metastatic Bladder Cancer: A Population-Based Study.

Purpose: Based on a large-population analysis, we aimed to estimate the incidence and survival of bone metastases (BM) in initial bladder cancer (BC) patients and to identify the risk and prognostic factors of BC patients with BM.Patients and methods: Using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, bladder cancer patients diagnosed between 2010 and 2014 were retrieved. Multivariate logistic and Cox regression analyses were employed to identify risk factors and prognostic factors for BM in BC patients. A Kaplan-Meier analysis with log-rank test was used to estimate the overall survival for BC and the difference between the survival curves.Results: A total of 1,223 (1.39%) BC patients were diagnosed with de novo BM. Variables such as age between 41 to 60 years, black race, unmarried status, higher T stage, higher N stage, poor tumour differentiation grade, lung metastases, liver metastases, and brain metastases were positively associated with BM occurrence. The median survival for BC patients with BM was dramatically decreased to 4.0 months. Factors including advanced age, absence of surgery, and presence of lung, liver, or brain metastases all predicted worse survival.Conclusion: BM can dramatically decrease the survival of bladder cancer patients. The findings of the present study can provide population-based identification of risk and prognostic factors for BC patients with BM at initial diagnosis, which can be used for BM occurrence prediction and individualized treatment plan-making.

Leupaxin Promotes Bladder Cancer Proliferation, Metastasis, and Angiogenesis Through the PI3K/AKT Pathway

Background/Aims: Leupaxin (LPXN) is a member of the paxillin protein family. Several studies have reported that LPXN regulates cancer development; however, the role of LPXN in bladder cancer remains unknown. Methods: The expression of LPXN in bladder cancer cells and tissues was determined by real-time PCR, western blotting, and immunohistochemistry, respectively. The biological role of LPXN in bladder cancer cell proliferation, invasion, and angiogenesis was explored both in vitro and in vivo. Results: LPXN expression was elevated in bladder cancer tissues and cell lines compared to adjacent non-tumor tissues and normal urothelial cells. High LPXN expression was correlated with large tumor size, advanced tumor stage, and poor survival in bladder cancer patients. Overexpression of LPXN significantly promoted the proliferation, invasion, and angiogenesis of bladder cancer cells, while suppressing LPXN had the opposite effects. The impact on tumor progression was abolished by inhibiting PI3K/ AKT signaling pathway. We further demonstrated that LPXN probably up-regulated S100P via the PI3K/AKT pathway. Conclusions: LPXN may facilitate bladder cancer progression by upregulating the expression of S100P via PI3K/AKT pathway. These results provide a novel insight into the role of LPXN in tumorigenesis and progression of bladder cancer and potential therapeutic target of bladder cancer.

Identification of Biomarkers Correlated with the TNM Staging and Overall Survival of Patients with Bladder Cancer.

Objective: To identify candidate biomarkers correlated with clinical prognosis of patients with bladder cancer (BC).Methods: Weighted gene co-expression network analysis was applied to build a co-expression network to identify hub genes correlated with tumor node metastasis (TNM) staging of BC patients. Functional enrichment analysis was conducted to functionally annotate the hub genes. Protein-protein interaction network analysis of hub genes was performed to identify the interactions among the hub genes. Survival analyses were conducted to characterize the role of hub genes on the survival of BC patients. Gene set enrichment analyses were conducted to find the potential mechanisms involved in the tumor proliferation promoted by hub genes.Results: Based on the results of topological overlap measure based clustering and the inclusion criteria, top 50 hub genes were identified. Hub genes were enriched in cell proliferation associated gene ontology terms (mitotic sister chromatid segregation, mitotic cell cycle and, cell cycle, etc.) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (cell cycle, Oocyte meiosis, etc.). 17 hub genes were found to interact with ≥5 of the hub genes. Survival analysis of hub genes suggested that lower expression of MMP11, COL5A2, CDC25B, TOP2A, CENPF, CDCA3, TK1, TPX2, CDCA8, AEBP1, and FOXM1were associated with better overall survival of BC patients. BC samples with higher expression of hub genes were enriched in gene sets associated with P53 pathway, apical junction, mitotic spindle, G2M checkpoint, and myogenesis, etc.Conclusions: We identified several candidate biomarkers correlated with the TNM staging and overall survival of BC patients. Accordingly, they might be used as potential diagnostic biomarkers and therapeutic targets with clinical utility.

YRNA expression predicts survival in bladder cancer patients

BackgroundNon-coding RNAs play an important role in human carcinogenesis. YRNAs (Ro-associated Y), a novel class of non-coding RNAs, have been identified as biomarker in various malignancies, but remain to be studied in urinary bladder cancer (BCA) patients.MethodsThe expression of all four YRNAs (RNY1, RNY3, RNY4, RNY5) was determined in archival BCA (urothelial carcinoma, n = 88) and normal urothelial bladder (n = 30) tissues using quantitative real-time PCR. Associations with clinicopathological parameters and prognostic role for overall and cancer-specific survival were analysed.ResultsAll YRNAs were significantly downregulated in BCA tissue. A low expression of RNY1, RNY3 and RNY4 was associated with muscle-invasive BCA, lymph node metastases and advanced grade. Furthermore, expression of RNY1 and RNY3 was predictive for BCA patients’ overall (also RNY4) and cancer-specific survival as estimated using Kaplan-Meier and univariate (but not multivariate) Cox regression analyses. RNY1, RNY3 and RNY4 show good discriminative ability between tumor and normal tissue, as well as between muscle-invasive and non-muscle-invasive urothelial carcinoma.ConclusionsThe expression of YRNAs is altered in BCA and associated with poor prognosis. Possible diagnostic role of YRNAs should be investigated in further studies.

Association of MMP-2, RB and PAI-1 with decreased recurrence-free survival and overall survival in bladder cancer patients.

BackgroundWe previously reported an accurate urine-based bladder cancer (BCa)-associated diagnostic signature that can be used to non-invasively detect BCa. In this study, we investigated whether a component of this signature could risk stratify patients with BCa.MethodsUtilizing immunohistochemistry, we investigated angiogenin, MMP-2, p53, RB and PAI-1 expression from 939 patients with BCa. The expression levels were scored by assigning a proportion score and an intensity score to yield a total staining score for each protein. The expressions of each protein individually and as an aggregate were then correlated with progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS).ResultsDifferential expressions of these markers were noted in BCa. With multivariate analysis in non-muscle invasive bladder cancer (NMIBC) age, tumor grade portended a worse PFS, while age, tumor grade, nodal status, MMP2, RB and PAI-1 expression portended a worse OS. As for multivariate analysis in muscle invasive bladder cancer (MIBC), age MMP-2 and RB were associated with a worse PFS, while age, nodal status, MMP-2, RB and PAI-1 were associated with a worse OS. Using Kaplan-Meier survival analysis, we noted a significant reduction in OS as more of the five biomarkers were expressed in a tumor. Thus, overall, high expressions of MMP-2, RB and/or PAI-1 in bladder tumors were markers of poor prognosis.ConclusionIndividually, MMP-2, RB and PAI-1, as well as in aggregate correlated with poor survival in patients with BCa. Thus, patients whose bladder tumors express these biomarkers may benefit from early radical treatment and/or neoadjuvant or adjuvant therapies.

The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a systematic review and meta-analysis.

The aim of this study was to evaluate the evidence regarding the neutrophil-to-lymphocyte ratio (NLR) as a factor predictive of survival in bladder cancer patients. A search of PubMed and Embase for relevant studies between January 1, 1966 and November 10, 2016 was performed with the terms [NLR OR (neutrophil lymphocyte ratio)] AND [(bladder cancer) OR BCa OR NMIBC OR MIBC]. Inclusion required studies published in English containing bladder cancer patients and evaluating NLR as a predictive factor. Endpoints of NLR and survival data were extracted for pooled analysis. The pooled results showed that an elevated NLR was a predictor for poor overall survival (OS) [hazard ratio (HR)=1.19, 95% confidence interval (CI) 1.07-1.31], cancer-specific survival (CSS) (HR=1.40, 95% CI 1.17-1.69), recurrence-free survival (RFS) (HR=1.58, 95% CI 1.24-2.03) and progression-free survival (PFS) (HR=1.33, 95% CI 1.19-1.49) in patients with bladder cancer. Heterogeneity between studies was observed for OS, CSS and RFS, but not for PFS. Publication bias was detected for all these outcomes. Our results showed that elevated NLR might be valuable as a predictive factor of survival in bladder cancer patients.

Neutrophil to Lymphocyte Ratio (NLR) at the Time of Transurethral Resection of Bladder Tumor: A Large Retrospective Study and Analysis of Racial Differences.

Introduction: Neutrophil/lymphocyte ratio (NLR) is an indicator of systemic inflammation and has been proven to be associated with an increased risk of extravesical disease, decreased cancer specific survival and overall survival in bladder cancer patients. A large proportion of healthy African Americans have a WBC count that is persistently lower than the normal range defined for individuals of European ancestry, this condition has been called “benign ethnic neutropenia”. The purpose of our study was to determine if NLR was different in patients of African ancestry (AA) vs European ancestry (EA) across different tumor grades and stages at the time of transurethral resection of bladder tumor(s) (TURBT).Materials and Methods: The records of consecutive patients who underwent TURBT were reviewed from the University of Wisconsin and the Atlanta Veterans’ Administration Medical Center (2000–2012). NLR was compared across tumor stage, tumor grade and ethnicity.Results: 297 consecutive patients met study criteria. 89% and 86%, were males and of European ancestry (EA) respectively. NLRs were different across T-stages (Ta-2.5, T1-3.9, T2-3.8; p = 0.001). but not across tumor grades in Ta (LG-2.5 vs HG-3.9, p = 0.57). EA had higher NLRs than AA (3.4 vs 1.9; p < 0.001).Conclusions: Higher NLRs appear to be associated with more advanced tumor stage at the time of TURBT. Patients of African ancestry have lower NLRs across all tumor stages compared to patients of European ancestry. Ethnicity should be taken into account when interpreting the NLR in patients with bladder cancer.

The prognostic significance of DAPK1 in bladder cancer.

Bladder cancer is one of the leading causes of cancer-related death in men, however, there was only limited effective treatment for invasive bladder cancer. DAPK1 has been shown to play important role in apoptosis and autophagy to suppress cancer progression. Previous results have shown that DAPK1 promoter was hypermethylated in the majority of bladder cancer specimens, however, the prognostic significance of DAPK1 in bladder cancer has yet to be demonstrated. In the present study, we found that DAPK1 expression was negatively associated with tumor stage and a low level expression of DAPK1 in bladder cancer specimens were associated with shorter survival in bladder cancer patients in 3 independent bladder cancer datasets (n = 462). Further investigation showed that FGFR3 knockdown resulted in downregulation of DAPK1 in bladder cancer cell line, suggesting that FGFR3 may be an upstream factor of DAPK1. Further analysis of the 3 independent bladder cancer datasets have identified ACOX1, UPK2, TRAK1, PLEKHG6 and MT1X genes had their expression significantly correlated with that of DAPK1. Knockdown of DAPK1 in bladder cancer T24 cells resulted in downregulation of ACOX1, UPK2 and TRAK1. Interestingly, TRAK1, by itself, was a favorable prognostic marker in the 3 independent bladder cancer datasets. Importantly, by using connectivity mapping with DAPK1-associated gene signature, we found that vemurafenib and trametinib could possibly reverse DAPK1-associated gene signature, suggesting that inhibition of Raf/MEK pathway may be a potential therapeutic approach for bladder cancer. Indeed, treatment of vemurafenib in T24 bladder cancer cells resulted in upregulation of DAPK1 confirming our connectivity mapping, while knockdown of DAPK1 resulted in reduced sensitivity towards inhibition of Braf signaling by vemurafenib. Together, our results suggest that DAPK1 is an important prognostic marker and therapeutic target for bladder cancer and have identified possible therapeutic agents for future testing in bladder cancer models with low DAPK1 expression.

MP10-12 EPIDEMIOLOGICAL TRENDS AND SOCIOECONOMIC DISPARITIES IN BLADDER CANCER SURVIVAL: ANALYSIS OF CALIFORNIA CANCER REGISTRY

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation II1 Apr 2017MP10-12 EPIDEMIOLOGICAL TRENDS AND SOCIOECONOMIC DISPARITIES IN BLADDER CANCER SURVIVAL: ANALYSIS OF CALIFORNIA CANCER REGISTRY Jeremy W. Martin, Nobel Nguyen, Jenny Chang, Rahul Dutta, Simone L. Vernez, Argyrios Ziogas, Hoda Anton-Culver, and Ramy F. Youssef Jeremy W. MartinJeremy W. Martin More articles by this author , Nobel NguyenNobel Nguyen More articles by this author , Jenny ChangJenny Chang More articles by this author , Rahul DuttaRahul Dutta More articles by this author , Simone L. VernezSimone L. Vernez More articles by this author , Argyrios ZiogasArgyrios Ziogas More articles by this author , Hoda Anton-CulverHoda Anton-Culver More articles by this author , and Ramy F. YoussefRamy F. Youssef More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.340AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Herein, we examined the California Cancer Registry (CCR) to determine bladder cancer survival disparities based on race, socioeconomic status (SES), insurance type, and tumor histopathology in California patients. METHODS The CCR was queried for bladder cancer cases in California from 1988 - 2012. Survival analyses were performed to determine the prognostic significance of racial and socioeconomic factors. Disease specific survival (DSS) of patients with squamous cell carcinoma (SCC) was compared to urothelial carcinoma (UCB). RESULTS 72,452 cases were included (75% men, 25% women). Median age was 72 (range 18 - 109). 81% were white, 3.8% black, 8.8% Hispanic, 5.2% Asian, and 1.2% others. SES was stratified by quintile. In black patients, tumors presented more frequently with non-urothelial histology, advanced stage, and high-grade and in females. Medicaid patients tended to be younger and have more advanced stage and high-grade tumors compared to those with Medicare or managed care (p < 0.0001). Kaplan-Meier analyses demonstrated significantly poorer 5-year DSS in black, low SES, Medicaid patients and in SCC compared to UCB (p < 0.0001). Multivariate analysis revealed that black race (DSS HR 1.295, 95% CI: 1.212 - 1.384), lowest SES (DSS HR 1.325, 95% CI: 1.259 - 1.395), Medicaid insurance (DSS HR 1.349, 95% CI: 1.246 - 1.460), and SCC histology (DSS HR 2.617 95% CI: 2.434 - 2.814) were all independent prognostic factors (all p < 0.0001) after controlling for stage, grade, age, and gender. CONCLUSIONS Analysis of California Cancer Registry demonstrated that black ethnicity, low SES, Medicaid insurance and squamous cell histology portend poorer disease-specific survival for bladder cancer patients in California, after adjusting for classic clinicopathological features. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e112-e113 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Jeremy W. Martin More articles by this author Nobel Nguyen More articles by this author Jenny Chang More articles by this author Rahul Dutta More articles by this author Simone L. Vernez More articles by this author Argyrios Ziogas More articles by this author Hoda Anton-Culver More articles by this author Ramy F. Youssef More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

HnRNP-L mediates bladder cancer progression by inhibiting apoptotic signaling and enhancing MAPK signaling pathways.

Heterogeneous nuclear ribonucleoprotein L (hnRNP-L) is a promoter of various kinds of cancers, but its actions in bladder cancer (BC) are unclear. In this study, we investigated the function and the underlying mechanism of hnRNP-L in bladder carcinogenesis. Our results demonstrated that enhanced hnRNP-L expression in BC tissues was associated with poor overall survival of BC patients. Depletion of hnRNP-L significantly suppressed cell proliferation in vitro and inhibited xenograft tumor growth in vivo. Furthermore, downregulation of hnRNP-L resulted in G1-phase cell cycle arrest and enhanced apoptosis accompanied by inhibition of EMT and cell migration. All these cellular changes were reversed by ectopic expression of hnRNP-L. Deletion of hnRNP-L resulted in decreased expression of Bcl-2, enhanced expression of caspases-3, -6 and -9 and inhibition of the MAPK signaling pathway. These findings demonstrate that hnRNP-L contributes to poor prognosis and tumor progression of BC by inhibiting the intrinsic apoptotic signaling and enhancing MAPK signaling pathways.

The Effect of Blood Groups and Rhesus Factor on Prognosis and Survival in Bladder Cancer Patients Underwent Radical Cystectomy

The Effect of Blood Groups and Rhesus Factor on Prognosis and Survival in Bladder Cancer Patients Underwent Radical Cystectomy

Occupational risk factors for relapse-free survival in bladder cancer patients

ABSTRACTThe influence of occupational risk factors on bladder cancer development is well investigated. However, studies on the influence on bladder cancer prognosis are rare. Therefore, it was of interest to investigate the time to first relapse in the follow-ups of three case-control series from Dortmund, Neuss, and Lutherstadt Wittenberg, Germany. Relapse-free survival of in total 794 urinary bladder cancer patients (Dortmund 174, Neuss 407, Lutherstadt Wittenberg 213) was derived from medical records. Cox regression models were used to determine the impact of profession and exposure to bladder carcinogens if the risk factor was present in at least four cases. One or several relapses were observed in 416 cases (52%). Median time to first relapse was 0.94 yr. Ten professions were observed in at least 4 patients. No significant associations were found. However, workers in the leather industry (n = 4), printing industry (n = 4), transportation (n = 43), and chemical industry (n = 40) and locksmiths/mechanics (n = 44) showed shorter relapse-free times. No trend to shorter relapse-free time was observed for miners (n = 42), agriculturists (n = 18), painters/lacquerers (n = 21), colorant production and processing workers (n = 7), foundry workers (n = 5), and persons exposed to aromatic amines (n = 45). Although the follow-up comprised nearly 800 cases, data on occupations and exposures of interest were not sufficient to obtain significant results. However, first results indicated potential associations that are worth further investigations.

116 - Early survival in bladder cancer patients following cystectomy: A prospective study

116 - Early survival in bladder cancer patients following cystectomy: A prospective study

114 - Preoperative anemia is a predictor of disease recurrence, cancer-specific survival and overall survival in bladder cancer patients: A retrospective study on 4335 radical cystectomies

114 - Preoperative anemia is a predictor of disease recurrence, cancer-specific survival and overall survival in bladder cancer patients: A retrospective study on 4335 radical cystectomies

Dysregulated expression of homebox gene HOXA13 is correlated with the poor prognosis in bladder cancer.

The homeobox (HOX) genes have been implicated playing important roles in many human cancers. HOXA13 is amember of HOX genes that encode transcription factors regulating embryonic development and cell fate. In the present study, we aimed to investigate the expression and prognostic significance of HOXA13 in bladder cancer. Immunohistochemical staining was initially performed to screen the differentially expressed HOXA13 between bladder cancer tissues and paired adjacent non-cancerous tissues. Subsequent Western blotting analysis validation was conducted using tissue samples from patients with bladder cancer. The expression level of HOXA13 was significantly higher in bladder cancer tissues compared to that in adjacent non-cancerous tissues (P< 0.001). The χ2-test showed that expression of HOXA13 was positively correlated with lymphatic metastasis (P= 0.013), bladder tumor TNM stage (P= 0.002) and pathological grade (P< 0.001). Kaplan-Meier survival analysis revealed that patients with bladder cancer with high expression of HOXA13 had shorter overall survival time (P= 0.001) and disease-free survival time (P= 0.001) compared to patients with low expression of HOXA13. Multivariate analysis indicated that HOXA13 was an independent prognostic factor for overall survival for bladder cancer patients. The results of our study show that high expression of HOXA13 is associated with the progression of bladder cancer and that HOXA13 might serve as abiomarker for prognosis of bladder cancer.

Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 in bladder cancer.

Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep‐sequencing revealed that two miRNA, microRNA‐139‐5p/microRNA‐139‐3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNA and their modulation of cancer networks in BC cells. Functional assays of BC cells were performed using transfection of mature miRNA or small interfering RNA (siRNA). Genome‐wide gene expression analysis, in silico analysis and dual‐luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan–Meier method. Gain‐of‐function studies showed that miR‐139‐5p and miR‐139‐3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR‐139‐5p and miR‐139‐3p. Kaplan–Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR‐139‐5p or miR‐139‐3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNA and might be a good prognostic marker for survival of BC patients.

MP61-02 ANTI-GLI1 AND ANTI-GLI2 AS NOVEL THERAPY TO INHIBIT BLADDER CANCER PROGRESSION

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II1 Apr 2016MP61-02 ANTI-GLI1 AND ANTI-GLI2 AS NOVEL THERAPY TO INHIBIT BLADDER CANCER PROGRESSION Peter A. Raven, Sebastian K. Frees, Betty B.H. Zhou, Claudia I. Chavez-Munoz, Michael E. Cox, and Alan I. So Peter A. RavenPeter A. Raven More articles by this author , Sebastian K. FreesSebastian K. Frees More articles by this author , Betty B.H. ZhouBetty B.H. Zhou More articles by this author , Claudia I. Chavez-MunozClaudia I. Chavez-Munoz More articles by this author , Michael E. CoxMichael E. Cox More articles by this author , and Alan I. SoAlan I. So More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.876AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The sonic hedgehog (SHH) signaling pathway regulates embryonic developmental processes such as pattern formation, differentiation, proliferation, and organogenesis. Studies have suggested that abnormal activation of the SHH pathway due to genomic alterations leads to an increase in cell survival and metastasis in cancer. High levels of hedgehog along with enhanced expression of hedgehog pathway target genes has been identified in different cancers such as bladder cancer (BC). Glioma-associated proteins (Gli), are a family of proteins which translocate to the nucleus to induce gene transcription. Expression levels of Gli have been interrelated with the expression levels of the SHH pathway, suggesting Gli transcriptional activity is a direct indicator of SHH pathway activity. Here we hypothesize that blockage of SHH pathway may be an efficacious way of stopping BC progression. METHODS SHH pathway protein expression was assessed by immunohistochemical staining in an in-house human BC tissue array comprising superficial, invasive and lymph node metastasized transitional cell carcinoma. In addition, a panel of BC cell lines was assessed for SHH pathway activation, function and responsiveness. Proliferation, cell death, migration and cell invasion were measured in response to small-molecule pathway inhibitors, and antisense oligonucleotides (ASO) targeted to Gli1 and 2. In-vitro ASO results were confirmed in an in-vivo murine non-muscle invasive BC model. RESULTS An array of human BC tissues showed SHH pathway activation through a significant upregulation of the SHH pathway proteins PTCH, SMO, and Gli1 and Gli2 in invasive BC when compared to non-invasive cancer and normal bladder tissue. Similarly, in a panel of urothelial carcinoma cells lines, Gli1 and Gli2 proteins were highly expressed in more aggressive cell lines (UM-UC3, T24) compared to less aggressive ones (RT4, SV-HUC). Inhibition of Gli1 and Gli2 signalling with ASO reduced tumor cell proliferation, migration and invasion in vitro in the more aggressive cell lines. In vivo, treatment of intravesical invasive tumors with Gli2 ASO significantly abrogated tumor growth when compared to control tumors. CONCLUSIONS Gli1 and Gli2 ASO may be a potential new therapy to stop progression and invasion of bladder cancer improving the survival of bladder cancer patients. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e803 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Peter A. Raven More articles by this author Sebastian K. Frees More articles by this author Betty B.H. Zhou More articles by this author Claudia I. Chavez-Munoz More articles by this author Michael E. Cox More articles by this author Alan I. So More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Hypoxia Marker GLUT-1 (Glucose Transporter 1) is an Independent Prognostic Factor for Survival in Bladder Cancer Patients Treated with Radical Cystectomy.

Background:Tumour hypoxia, which is frequent in many cancer types, is associated with treatment resistance and poor prognosis. The role of hypoxia in surgically treated bladder cancer (BC) is not well described. We studied the role of hypoxia in two independent series of urothelial bladder cancers treated with radical cystectomy.Methods:279 patients from the University Hospital Network (UHN), Toronto, Canada, and Turku University, Finland were studied. Hypoxia biomarkers (HIF1-α, CAIX, GLUT-1) and proliferation marker Ki-67 were analyzed with immunohistochemistry using defined tissue microarrays. Kaplan-Meier methods and Cox proportional hazards regression models were used to investigate prognostic role of the factors.Results:In univariate analyses, strong GLUT-1 positivity and a high Ki-67 index were associated with poor survival. In multivariate model containing clinical prognostic variables, GLUT-1 was an independent prognostic factor associated with worse disease-specific survival (HR 2.9, 95% CI 0.7–12.6, Wald p = 0.15 in the Toronto cohort and HR 3.2, 95% CI 1.3–7.5, Wald p = 0.0085 in the Turku cohort).Conclusion:GLUT-1 is frequently upregulated and is an independent prognostic factor in surgically treated bladder cancer. Further studies are needed to evaluate the potential role of hypoxia-based and targeted therapies in hypoxic bladder tumours.

Expression of long noncoding RNA lncRNA-n336928 is correlated with tumor stage and grade and overall survival in bladder cancer

Long noncoding RNAs (lncRNAs) have been implicated playing important roles in human urologic cancers. In the present study, microarray analysis was initially performed to screen the differentially expressed lncRNAs between bladder cancer tissues and paired adjacent non-cancerous tissues (n = 3). Subsequent qRT-PCR validation was conducted using tissue samples from 95 patients with bladder cancer. Results showed that the expression level of lncRNA-n336928 (noncode database ID: n336928) was significantly higher in bladder cancer tissues compared to that in adjacent noncancerous tissues (P < 0.001). Chi-square test showed that expression of lncRNA-n336928 was positively correlated with bladder tumor stage and histological grade (P < 0.001). Kaplan–Meier survival analysis revealed that patients with bladder cancer with high expression of lncRNA-n336928 had shorter overall survival time compared to the patients with low expression of lncRNA-n336928. Multivariate analysis indicated that lncRNA-n336928 was an independent prognostic factor for overall survival for bladder cancer patients. Collectively, our study shows that high expression of lncRNA-n336928 is associated with the progression of bladder cancer, and that lncRNA-n336928 might serve as a biomarker for prognosis of bladder cancer.

CXCL5 is a potential diagnostic and prognostic marker for bladder cancer patients.

Chemokine C-X-C motif ligand 5 (CXCL5) is critical for bladder cancer growth and progression. Our previous study demonstrated that increase of CXCL5 in bladder cancer cell lines had an effect on tumor growth and progression. This study aims to investigate the expression of CXCL5 in tissue and urine of bladder cancer patients, in relation to clinicopathologic parameters, and as a predictive value in diagnosing and evaluating bladder cancer. Urothelial bladder cancer tissues from 255 patients were profiled for CXCL5 alterations by immunohistochemistry. Urine samples collected from patients with bladder cancer and urinary tract infections as well as healthy volunteers were analyzed by ELISA. High expression of CXCL5 in bladder cancer tissue was correlated with TNM stage (P = 0.012), cancer grade (P = 0.001), and lymph node metastasis (P = 0.007). CXCL5 alterations were associated with overall survival (P = 0.007), progression free survival (P = 0.004), and recurrence free survival in muscle invasive bladder cancers (P = 0.026). CXCL5 expression in the urine of bladder cancer patients was significantly different from urinary tract infection patients (P = 0.001) and healthy volunteers. However, urine leukocytes may predict CXCL5 levels (β = 0.56, P < 0.001, R (2) = 0.314). CXCL5 expression in urine was also related to bladder cancer TNM stage (P = 0.039), lymph node metastasis (P = 0.023), tumor size (P = 0.007), and tumor grade (P = 0.005). The sensitivity and specificity for CXCL5/creatinine in predicting bladder cancer were 80.4 and 61.3%, respectively. These results suggest increased CXCL5 expression in cancer tissue predicts poor survival in bladder cancer patients. CXCL5 expression in urine is useful in a minimally invasive modality for bladder cancer diagnosis. However, urine leukocytes are significant predictors of CXCL5 levels and may affect its result in bladder cancer diagnosis.