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 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 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.

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 Prognostic Relevance of Promoter Hypermethylation of Multiple Genes in Breast Cancer Patients

2009 ◽  
Vol 31 (6) ◽  
pp. 487-500
Author(s):  
Gayatri Sharma ◽  
Sameer Mirza ◽  
Yi-Hsin Yang ◽  
Rajinder Parshad ◽  
Priya Hazrah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Methylation Status ◽  
Promoter Hypermethylation ◽  
Aberrant Methylation ◽  
Breast Cancers ◽  
Cox Regression Analysis ◽  
Disease Prognosis ◽  
Multiple Genes ◽  
The Impact

Background: Methylation-mediated suppression of detoxification, DNA repair and tumor suppressor genes has been implicated in cancer development. This study was designed to investigate the impact of concurrent methylation of multiple genes in breast tumors on disease prognosis.Methods: Methylation specific PCR was carried out to analyze the methylation status of seven genes in archived breast tissues and determine the effect of aberrant methylation of multiple genes on disease prognosis and patients’ survival.Results: Promoter hypermethylation was observed in PRB 67%, ERα 64%, RASSF1A 63%, p16INK4A 51%, PRBβ2 22%, GSTP1 25% and BRCA1 27% of the breast cancers, respectively. Concurrent methylation of BRCA1, ERα, GSTP1 and RARβ2, was observed in a large proportion of breast cancers analyzed, suggesting that these genes do not appear to be methylated alone. Patients with high methylation indices had poor prognosis (p < 0.001, Hazards ratio = 14.58). Cox regression analysis showed RARβ2 promoter methylation to be an independent important determinant of breast cancer prognosis.Conclusions: Our results suggest that methylation of multiple genes plays an important role in prognosis of breast cancer. Our study not only describes the association of methylation mediated silencing of multiple genes with the severity of disease, but also drives to speculate the molecular crosstalk between genes or genetic pathways regulated by them individually.

scholarly journals CCL2 is associated with metastasis and poor prognosis of bladder cancer

2019 ◽  
Author(s):  
wei gao ◽  
qiwang zhang ◽  
lianhua zhang ◽  
qiang liu ◽  
xuehui duan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Regression Models ◽  
Cox Regression ◽  
Tumor Grade ◽  
The Novel ◽  
Kaplan Meier ◽  
Ccl2 Expression ◽  
Immune Factor ◽  
Cancer Types

Abstract Background: Chemokine (C-C motif) ligand 2 (CCL2) is an important immune factor, which may be important in cancer progression by promoting proliferation, invasion metastasis and the tumor microenvironment. Recent researches have demonstrated that overexpression of CCL2 is associated with unfavorable prognosis in various cancer types. In this study, we aim to determine the prognostic value of CCL2 expression in patients with bladder cancer (BC). Methods: We retrospectively enrolled 154 patients with bladder cancer at Renji Hospital, Shanghai Jiaotong University between 2005 and 2007. CCL2 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and prognosis were evaluated. Kaplan-Meier method was applied to compare survival curves. Cox regression models were fitted to analyze the effect of prognostic factors on Overall survival (OS). Results: CCL2 protein had high expression in 73 of 154 cases of BC (47%). CCL2 overexpression was significantly associated with tumor grade (P<0.001), stage (P=0.005), and lymph node metastasis (P=0.025). The Kaplan–Meier survival analysis demonstrated that CCL2 expression was significantly associated with DSS and OS (both P< 0.001). Multivariate analysis further demonstrated that CCL2 was an independent prognostic factor for patients with BC. Conclusion: CCL2 might be a new molecular marker to predict the prognosis of patients with BC. The novel risk classification based on combining CCL2 and TNM is more reliable than using either alone.

Social disparities in the diagnosis and management of bladder cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 403-403
Author(s):  
Shaakir Hasan ◽  
Stanislav Lazarev ◽  
Madhur Garg ◽  
Robert H. Press ◽  
Arpit Chhabra ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Regression Analysis ◽  
Cox Regression ◽  
Multinomial Logistic Regression ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Demographic Factors ◽  
Cox Regression Analysis ◽  
Diagnosis And Management ◽  
Muscle Invasive

403 Background: The socioeconomic characteristics associated with the diagnosis and management of bladder cancer are not well described. Methods: We utilized the National Cancer Database (NCDB) to stratify cases of urothelial cell carcinoma of the bladder by the National Comprehensive Cancer Network (NCCCN) guidelines: early (Tis, Ta, T1), muscle invasive (T2-T3, N0), locally advanced (T4, N1-3), and metastatic. We then used multivariate binomial and multinomial logistic regression analyses to identify demographic characteristics associated with stage at diagnosis and receipt of cancer-directed therapies. Hazard ratios (HR) are reported with 95% confidence intervals. Results: After exclusions, we identified 331,714 early, 72,154 muscle invasive, 15,579 locally advanced, and 15,161 metastatic cases. Relative to diagnosis at early stage, the two strongest independent predictors of diagnosis at muscle invasive, locally advanced, and metastatic disease included black race (HR = 1.19 [1.15-1.23], HR = 1.49 [1.40-1.59], HR = 1.66 [1.56-1.76], respectively), and female gender (HR = 1.21 [1.18-1.21], HR = 1.16 [1.12-1.20], and HR = 1.34 [1.29-1.38], respectively). Additional demographic factors associated with diagnosis at a more advanced stage on multivariable analysis included older age, treatment at an academic center (except for metastasis), Medicaid insurance, and patients from lower income/ less educated/more rural areas (all p < 0.01). The following demographic factors were less likely to receive cancer-directed therapies, signified by odds ratios, per multivariable binomial regression analysis: Additionalyl, female patients (HR = 1.03, 1.02-1.05) and black patients (HR = 1.13, 1.11-1.16) were the only demographic correlates of reduced survival in the entire cohort with multivariable cox regression analysis. Conclusions: In the largest study of its kind, we report that several socioeconomic, racial, and gender factors are associated with the diagnosis of bladder cancer at a later stage, as well as the use of less cancer-directed treatments. Further investigation is warranted to better characterize, and ultimately improve upon, health disparities in bladder cancer. Research Sponsor: None[Table: see text]

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 The Interplay between Oxidative Phosphorylation and Glycolysis as a Potential Marker of Bladder Cancer Progression

2020 ◽  
Vol 21 (21) ◽  
pp. 8107 ◽  
Author(s):  
Greta Petrella ◽  
Giorgia Ciufolini ◽  
Riccardo Vago ◽  
Daniel Oscar Cicero
Keyword(s):  
Bladder Cancer ◽  
Oxidative Phosphorylation ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cancer Genomics ◽  
Low Grade ◽  
Metabolic State ◽  
Extracellular Medium ◽  
Potential Marker ◽  
Risk Of Progression

Urothelial bladder cancer (UBC) is the most common tumor of the urinary system. One of the biggest problems related to this disease is the lack of markers that can anticipate the progression of the cancer. Genomics and transcriptomics have greatly improved the prediction of risk of recurrence and progression. Further progress can be expected including information from other omics sciences such as metabolomics. In this study, we used 1H-NMR to characterize the intake of nutrients and the excretion of products in the extracellular medium of three UBC cell lines, which are representatives of low-grade tumors, RT4, high-grade, 5637, and a cell line that shares genotypic features with both, RT112. We have observed that RT4 cells show an activated oxidative phosphorylation, 5637 cells depend mostly on glycolysis to grow, while RT112 cells show a mixed metabolic state. Our results reveal the relative importance of glycolysis and oxidative phosphorylation in the growth and maintenance of different UBC cell lines, and the relationship with their genomic signatures. They suggest that cell lines associated with a low risk of progression present an activated oxidative metabolic state, while those associated with a high risk present a non-oxidative state and high glycolytic activity.

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