scholarly journals Clinical Implications and Prognostic Values ofProstate Cancer Susceptibility CandidateMethylation in Primary Nonmuscle Invasive Bladder Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Young-Won Kim ◽  
Hyung-Yoon Yoon ◽  
Sung Pil Seo ◽  
Sang Keun Lee ◽  
Ho Won Kang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cox Regression ◽  
Cancer Susceptibility ◽  
Methylation Status ◽  
High Rate ◽  
Invasive Bladder Cancer ◽  
Clinicopathological Parameters ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Nonmuscle Invasive Bladder Cancer

DNA methylation is the most common and well-characterized epigenetic change in human cancer. Recently, an association betweenprostate cancer susceptibility candidate(PRAC) methylation and genitourinary cancer was proposed. The aim of the present study was to evaluate the association betweenPRACmethylation status and clinicopathological parameters and prognosis in long-term follow-up primary nonmuscle invasive bladder cancer (NMIBC). The clinical relevance ofPRACmethylation was determined in 136 human bladder specimens (eight normal controls [NCs] and 128 primary NMIBCs) using quantitative pyrosequencing analysis.PRACmethylation was significantly higher in NMIBC patients than in NCs and was significantly associated with higher grade and more advanced stage of cancer. Kaplan-Meier estimates revealed significant difference in tumor recurrence and progression according toPRACmethylation status (bothp< 0.05). Multivariate Cox regression analysis revealed that thePRACmethylation status was a strong predictor of recurrence (hazard ratio [HR], 2.652;p= 0.012) and progression (HR, 9.531;p= 0.035) of NMIBC. Enhanced methylation status ofPRACwas positively associated with a high rate of recurrence and progression in NMIBC patients, suggesting thatPRACmethylation may be a promising prognostic marker of NMIBC.

Prognostic utility of the combination of pretreatment monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with NMIBC after transurethral resection

2019 ◽  
Vol 13 (18) ◽  
pp. 1543-1555
Author(s):  
Qinghai Wang ◽  
Tao Huang ◽  
Jianlei Ji ◽  
Hongyang Wang ◽  
Chen Guo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transurethral Resection ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Predictive Biomarker ◽  
Neutrophil To Lymphocyte Ratio ◽  
Invasive Bladder Cancer ◽  
Lymphocyte Ratio ◽  
Prognostic Utility ◽  
Nonmuscle Invasive Bladder Cancer

Aim: To investigate and validate predictive value of combination of pretreatment monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) for disease free survival (DFS) and overall survival (OS) in nonmuscle invasive bladder cancer after transurethral resection. Materials & methods: Total 358 patients enrolled were assigned into three (MLR-NLR 0, 1 and 2) groups per the cut-off values of MLR and NLR. Results: Kaplan–Meier curves showed MLR, NLR and their combination were statistically associated with DFS (p < 0.001) and OS (p < 0.001). Univariate and multivariate COX regression analyses revealed that combination of MLR with NLR was an independent prognostic predictor for both DFS (HR: 3.080; 95% CI: 1.870–5.074; p < 0.001 for MLR-NLR 2 vs MLR-NLR 0) and OS (HR: 2.815; 95% CI: 1.778–4.456; p < 0.001 for MLR-NLR 2 vs MLR-NLR 0). Calibration plots and decision curve analysis exhibited combination of MLR and NLR had good calibration accuracy with potential clinical usefulness. Conclusion: Combined MLR and NLR is a prognostic predictive biomarker in nonmuscle invasive bladder cancer after transurethral resection.

Unraveling UCA1 lncRNA prognostic utility in urothelial bladder cancer

2019 ◽  
Vol 40 (8) ◽  
pp. 965-974 ◽  
Author(s):  
Margaritis Avgeris ◽  
Anastasia Tsilimantou ◽  
Panagiotis K Levis ◽  
Theodoros Rampias ◽  
Maria-Alexandra Papadimitriou ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Benefit ◽  
Prediction Models ◽  
Cox Regression ◽  
Invasive Bladder Cancer ◽  
Precision Oncology ◽  
Muscle Invasive Bladder Cancer ◽  
Bootstrap Analysis ◽  
Cox Regression Analysis ◽  
Muscle Invasive

AbstractIn the era of precision oncology, bladder cancer (BlCa) is characterized by generic patient management and lack of personalized prognosis and surveillance. Herein, we have studied the clinical significance of urothelial cancer associated 1 (UCA1) lncRNA in improving patients’ risk stratification and prognosis. A screening cohort of 176 BlCa patients was used for UCA1 quantification. The Hedegaard et al. (n = 476) and The Cancer Genome Atlas (TCGA) provisional (n = 413) were analyzed as validation cohorts for non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), respectively. Patients’ survival outcome was assessed using recurrence and progression for NMIBC or death for MIBC as clinical endpoint events. Bootstrap analysis was performed for internal validation of Cox regression analysis, whereas the clinical benefit of disease prognosis was assessed by decision curve analysis. UCA1 was significantly overexpressed in bladder tumors compared with normal urothelium, which was confirmed only in the case of NMIBC. Interestingly, reduced expression of UCA1 was correlated with muscle-invasive disease as well as with tumors of higher stage and grade. UCA1 loss was strongly associated with higher risk of short-term relapse [hazard ratio (HR) = 1.974; P = 0.032] and progression to invasive stages (HR = 3.476; P = 0.023) in NMIBC. In this regard, Hedegaard et al. and TCGA validation cohorts confirmed the unfavorable prognostic nature of UCA1 loss in BlCa. Finally, prognosis prediction models integrating UCA1 underexpression and established clinical disease markers contributed to improved stratification specificity and superior clinical benefit for NMIBC prognosis. Underexpression of UCA1 correlates with worse disease outcome in NMIBC and contributes to superior prediction of disease early relapse and progression as well as improved patient stratification specificity.

scholarly journals ASSESSMENT OF A PROGNOSTIC VALUE OF CDKN2A AND TIMP3 GENE METHYLATION IN BLADDER CANCER

2018 ◽  
Vol 15 (3) ◽  
pp. 263-275
Author(s):  
M. P. Smal ◽  
N. V. Nikitchenko ◽  
A. I. Rolevich ◽  
T. I. Nabebina ◽  
S. A. Krasny ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Prognostic Value ◽  
Cox Regression ◽  
Methylation Status ◽  
Morphological Characteristics ◽  
Promoter Hypermethylation ◽  
Epigenetic Changes ◽  
Gene Methylation ◽  
Cox Regression Analysis

Promoter hypermethylation of tumor suppressor genes is one of the mechanisms of epigenetic regulation disturbance of gene expression and is often observed in different cancer types. The profile of mutational and epigenetic changes characterizes a malignant potential of a tumor, as well as its ability to invade and metastasize.The aim of the study was to determine a prognostic value of p16, p14ARF and TIMP3 gene methylation in the group of 158 bladder cancer patients. Epigenetic changes in these genes were observed with a frequency of 11.4, 0 and 10.8 %, respectively, and did not depend on clinic-morphological characteristics.A statistically significant association of p16 and TIMP3 abnormal methylation with smoking was found, indicating a possible influence of tobacco smoke carcinogens on the occurrence of these epigenetic changes. In the multivariate Cox regression analysis, p16 promoter hypermethylation was an independent predictor for bladder cancer progression (HR 6.84; 95 % CI 1.6–29.9; р = 0.011).The use of the data on the p16 methylation status may improve the accuracy of prognosis of the bladder cancer clinical course and the selection of appropriate treatment strategy.

scholarly journals GSTT1as a Prognosticator for Recurrence and Progression in Patients with Non-Muscle-Invasive Bladder Cancer

2010 ◽  
Vol 29 (2) ◽  
pp. 81-87 ◽  
Author(s):  
Yun-Sok Ha ◽  
Chunri Yan ◽  
Min Su Lym ◽  
Pildu Jeong ◽  
Won Tae Kim ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Invasive Bladder Cancer ◽  
Clinicopathological Parameters ◽  
Rank Test ◽  
Glutathione S Transferase ◽  
Muscle Invasive Bladder Cancer ◽  
Gstt1 Null Genotype ◽  
Muscle Invasive

Although polymorphisms in glutathione S-transferase (GST) have been associated with the risk of bladder cancer (BC), few reports provide information about the development of BC. The aim of the present study was to investigate the effect of homozygous glutathione S-transferase-μ (GSTM1) and glutathione S-transferase-&phis; (GSTT1) deletions as prognostic markers in non-muscle-invasive bladder cancer (NMIBC). A total of 241 patients with primary NMIBC were enrolled in this study. GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR) using blood genomic DNA. The results were compared with clinicopathological parameters. The prognostic significance of the GSTs was evaluated by Kaplan-Meier and multivariate Cox regression model. A statistically significant association between genotype and histopathological parameter was not observed. The patients with the GSTT1-positive genotype had significantly reduced recurrence- and progression-free survival than those with the GSTT1-null genotype (log-rank test,p< 0.05, respectively). Recurrenceand progressionfree survival were not related to the GSTM1 genotypes. In multivariate regression analysis, the GSTT1positive genotype was the independent predictor for recurrence [hazard ratio (HR), 1.631;p= 0.043] and progression (HR, 3.418;p= 0.006). These results suggested that the GSTT1 genotype could be a useful prognostic marker for recurrence and progression in NMIBC.

scholarly journals Intravesical bacillus Calmette-Guérin versus chemohyperthermia for high-risk non-muscle-invasive bladder cancer

2015 ◽  
Vol 9 (5-6) ◽  
pp. 278 ◽  
Author(s):  
Rahmi Gokhan Ekin ◽  
Ilker Akarken ◽  
Ferruh Zorlu ◽  
Huseyin Tarhan ◽  
Ulku Kucuk ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Propensity Score ◽  
Cox Regression ◽  
Invasive Bladder Cancer ◽  
Bacillus Calmette Guerin ◽  
Muscle Invasive Bladder Cancer ◽  
Free Interval ◽  
Significant Difference ◽  
Muscle Invasive

Introduction: Patients with high-risk non-muscle invasive bladder cancer (NMIBC) need adjuvant intravesical treatment after surgery. Although bacillus Calmette-Guérin (BCG) is highly effective, new adjuvant treatments to decrease recurrences and toxicity have been studies. We performed a retrospective propensity score-matched study to compare the efficacy of BCG and chemohyperthermia (C-HT).Methods: We included 1937 patients diagnosed with bladder cancer between January 2004 and January 2014. The primary efficacy endpoint was recurrence-free interval. Patients treated with C-HT were matched with patients treated with BCG using propensity score- matched analysis. Cox-regression models were used to estimate the association between intravesical treatments and the presence of recurrence and progression.Results: Of the 710 patients treated with intravesical treatments, 40 and 142 were eligible for inclusion in C-HT and BCG groups, respectively. Following case matching, there were no differences in patient or tumour characteristics between treatment groups. The 2-year recurrence-free interval in C-HT and BCG groups were 76.2% and 93.9%, respectively (p = 0.020). C-HT treatment (hazard ratio [HR] 5.42; 95% confidence interval [CI] 1.11–26.43; p = 0.036) and high-grade tumour (HR 4.60; 95% CI 1.01–20.88; p = 0.048) are associated with an elevated odds of tumour recurrence. In multivariate Cox-regression analysis, there was no significant difference between C-HT and BCG in the odds of recurrence (p = 0.054). There were no differences in progression between C-HT and BCG.Conclusion: C-HT is not as effective treatment as BCG in high-risk NMIBC patients who are BCG-naive. Although, there were no significant difference in the odds of recurrence, recurrence-free interval is significantly improved by the administration of BCG.

scholarly journals Identification of a Nuclear Mitochondrial-Related Multi-Genes Signature to Predict the Prognosis of Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xuewen Jiang ◽  
Yangyang Xia ◽  
Hui Meng ◽  
Yaxiao Liu ◽  
Jianfeng Cui ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Genome Database ◽  
Cox Regression Analysis ◽  
Muscle Invasive

IntroductionBladder cancer (BC) is one of the most prevalent urinary cancers, and its management is still a problem causing recurrence and progression, elevating mortality.Materials and MethodsWe aimed at the nuclear mitochondria-related genes (MTRGs), collected from the MITOMAP: A Human Mitochondrial Genome Database. Meanwhile, the expression profiles and clinical information of BC were downloaded from the Cancer Genome Atlas (TCGA) as a training group. The univariate, multivariate, and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to construct a nuclear mitochondrial-related multi-genes signature and the prognostic nomogram.ResultsA total of 17 nuclear MTRGs were identified to be correlated with the overall survival (OS) of BC patients, and a nuclear MTRGs signature based on 16 genes expression was further determined by the LASSO Cox regression analysis. Based on a nuclear MTRGs scoring system, BC patients from the TCGA cohort were divided into high- and low- nuclear MTRGs score groups. Patients with a high nuclear MTRGs score exhibited a significantly poorer outcome (median OS: 92.90 vs 20.20 months, p&lt;0.0001). The nuclear MTRGs signature was further verified in three independent datasets, namely, GSE13507, GSE31684, and GSE32548, from the Gene Expression Omnibus (GEO). The BC patients with a high nuclear MTRGs score had significantly worse survival (median OS in GSE13507: 31.52 vs 98.00 months, p&lt;0.05; GSE31684: 32.85 months vs unreached, p&lt;0.05; GSE32548: unreached vs unreached, p&lt;0.05). Furthermore, muscle-invasive bladder cancer (MIBC) patients had a significantly higher nuclear MTRGs score (p&lt;0.05) than non-muscle-invasive bladder cancer (NMIBC) patients. The integrated signature outperformed each involved MTRG. In addition, a nuclear MTRGs-based nomogram was constructed as a novel prediction prognosis model, whose AUC values for OS at 1, 3, 5 years were 0.76, 0.75, and 0.75, respectively, showing the prognostic nomogram had good and stable predicting ability. Enrichment analyses of the hallmark gene set and KEGG pathway revealed that the E2F targets, G2M checkpoint pathways, and cell cycle had influences on the survival of BC patients. Furthermore, the analysis of tumor microenvironment indicated more CD8+ T cells and higher immune score in patients with high nuclear MTRGs score, which might confer sensitivity to immune checkpoint inhibitors.ConclusionsNot only could the signature and prognostic nomogram predict the prognosis of BC, but it also had potential therapeutic guidance.

scholarly journals Calculated identification of mutator-derived lncRNA signatures of genomic instability to predict the clinical outcome of muscle-invasive bladder cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yingchun Liang ◽  
Fangdie Ye ◽  
Zhang Cheng ◽  
Yuxi Ou ◽  
Lujia Zou ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Genomic Instability ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Differentially Expressed ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Cox Regression Analysis ◽  
Muscle Invasive

Abstract Background Muscle-invasive bladder cancer (MIBC) is one of the most important type of bladder cancer, with a high morbidity and mortality rate. Studies have found that long non-coding RNA (lncRNA) plays a key role in maintaining genomic instability. However, Identification of lncRNAs related to genomic instability (GIlncRNAs) and their clinical significance in cancers have not been extensively studied yet. Methods Here, we downloaded the lncRNA expression profiles, somatic mutation profiles and clinical related data in MIBC patients from The Cancer Genome Atlas (TCGA) database. A lncRNA computational framework was used to find differentially expressed GIlncRNAs. Multivariate Cox regression analysis was used to construct a genomic instability-related lncRNA signature (GIlncSig). Univariate and multivariate Cox analyses were used to assess the independent prognostic for the GIlncSig and other key clinical factors. Results We found 43 differentially expressed GIlncRNAs and constructed the GIlncSig with 6 GIlncRNAs in the training cohort. The patients were divided into two risk groups. The overall survival of patients in the high-risk group was lower than that in the low-risk group (P < 0.001), which were further verified in the testing cohort and the entire TCGA cohort. Univariate and multivariate Cox regression showed that the GIlncSig was an independent prognostic factor. In addition, the GIlncSig correlated with the genomic mutation rate of MIBC, indicating its potential as a measure of the degree of genomic instability. The GIlncSig was able to divide FGFR3 wild- and mutant-type patients into two risk groups, and effectively enhanced the prediction effect. Conclusion Our study introduced an important reference for further research on the role of GIlncRNAs, and provided prognostic indicators and potential biological therapy targets for MIBC.

scholarly journals INFLUENCE OF P16 GENE METHYLATION ON THE RISK OF PROGRESSION OF NON-MUSCLE INVASIVE BLADDER CANCER

2018 ◽  
Vol 62 (3) ◽  
pp. 322-328
Author(s):  
M. P. Smal ◽  
N. V. Nikitchenko ◽  
A. I. Rolevich ◽  
T. I. Nabebina ◽  
S. A. Krasny ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Cox Regression ◽  
Methylation Status ◽  
Tumor Grade ◽  
Promoter Hypermethylation ◽  
Epigenetic Changes ◽  
Cox Regression Analysis ◽  
Risk Of Progression ◽  
Muscle Invasive

To accurately predict the tumor behavior and individualize the treatment approach, new methods for bladder cancer (BC) prognosis are required. The most promising prognostic markers are the mutational and epigenetic changes of genes involved in maintaining cellular homeostasis. In the present study, we evaluated the influence of p16 promoter hypermethylation on the risk of recurrence, progression and disease outcome in the group of 158 BC patients. p16 epigenetic changes were found in 11.4 % of urothelial carcinomas and did not depend on clinicоmorphological characteristics. However, in the subgroup of patients with non-muscle invasive tumors, p16 abnormal methylation was significantly associated with smoking, and in the subgroup of patients with muscle-invasive BC, it was linked to a high tumor grade (G3). In the multivariate Cox regression analysis, p16 promoter hypermethylation was an independent predictor for bladder cancer progression (HR 6.84; 95 % CI 1.6–29.9; р = 0.011). The use of the data on the p16 methylation status may improve the accuracy of prognosis of the bladder cancer clinical course and the selection of appropriate treatment strategy.

scholarly journals Prognostic Value of Preoperative Inflammation Markers in Non-Muscle Invasıve Bladder Cancer

2020 ◽  
Author(s):  
Hüseyin Alperen Yıldız ◽  
Dogan Deger ◽  
Guven Aslan
Keyword(s):  
Bladder Cancer ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Cost Effective ◽  
Invasive Bladder Cancer ◽  
Clinicopathological Parameters ◽  
Muscle Invasive Bladder Cancer ◽  
Neutrophil Lymphocyte Ratio ◽  
Muscle Invasive ◽  
The Relationship

Purpose: To investigate the prediction values of the preoperative NLR, LMR, PLR, MPV, RDW for recurrence and progression of patients with non-muscle invasive bladder cancer (NMIBC). Methods: In this prospective study, 94 consecutive patients, newly diagnosed with NMIBC between July 2017 - August 2018 were included. The blood samples were collected from patients before transurethral resection of bladder tumor (TURB) and NLR, LMR, PLR, RDW, MPV values were calculated. The effect of these preoperative inflammatory parameters and other clinicopathological parameters on recurrence and progression rates were evaluated. Kaplan-Meier and multivariate Cox regression analyses were performed to identify significant prognostic variables. Results: The mean follow-up was 11 ± 6.4 months. Recurrence was observed in 35.1% and progression was detected in 7.4% of the patients. Neutrophil-lymphocyte ratio was statistically significantly associated with both recurrence (p = 0.01) and progression (p = 0.035) whereas lymphocyte-monocyte ratio was only associated with recurrence (p = 0.038). In the survival analyses, the relationship between recurrence and LMR was confirmed in both univariate (p = 0.021) and multivariate (p = 0.022) analyses. The relationship between NLR and recurrence was confirmed in univariate analysis (p = 0.019), however in multivariate analysis was found to be statistically insignificant (p = 0.051). Conclusions: Lymphocyte-monocyte ratio might be an easy obtainable, non-invasive and cost-effective method for predicting recurrence of disease in patients with non-muscle invasive bladder cancer.

Predictive Model for Live Birth at 12 Months After Starting In-Vitro Fertilization Treatment

MedPharmRes ◽  
2018 ◽  
Vol 2 (2) ◽  
pp. 5-20
Author(s):  
Vu Ho ◽  
Toan Pham ◽  
Tuong Ho ◽  
Lan Vuong
Keyword(s):  
In Vitro Fertilization ◽  
Live Birth ◽  
Cox Regression ◽  
Financial Burden ◽  
Oocyte Retrieval ◽  
Operating Characteristics ◽  
Vitro Fertilization ◽  
Cox Regression Analysis ◽  
Significant Difference

IVF carries a considerable physical, emotional and financial burden. Therefore, it would be useful to be able to predict the likelihood of success for each couple. The aim of this retrospective cohort study was to develop a prediction model to estimate the probability of a live birth at 12 months after one completed IVF cycle (all fresh and frozen embryo transfers from the same oocyte retrieval). We analyzed data collected from 2600 women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) at a single center in Vietnam between April 2014 and December 2015. All patients received gonadotropin-releasing hormone (GnRH) antagonist stimulation, followed by fresh and/or frozen embryo transfer (FET) on Day 3. Using Cox regression analysis, five predictive factors were identified: female age, total dose of recombinant follicle stimulating hormone used, type of trigger, fresh or FET during the first transfer, and number of subsequent FET after the first transfer. The area under the receiver operating characteristics curve for the final model was 0.63 (95% confidence interval [CI] 0.60‒0.65) and 0.60 (95% CI 0.57‒0.63) for the validation cohort. There was no significant difference between the predicted and observed probabilities of live birth (Hosmer-Lemeshow test, p > 0.05). The model developed had similar discrimination to existing models and could be implemented in clinical practice.

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