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 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<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<0.05; GSE31684: 32.85 months vs unreached, p<0.05; GSE32548: unreached vs unreached, p<0.05). Furthermore, muscle-invasive bladder cancer (MIBC) patients had a significantly higher nuclear MTRGs score (p<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 Modified Glasgow prognostic score can predict survival of muscle invasive bladder cancer patients after radiotherapy

2020 ◽  
Vol 61 (4) ◽  
pp. 616-621
Author(s):  
Koyo Kikuchi ◽  
Ryuji Nakamura ◽  
Takafumi Segawa ◽  
Hirobumi Oikawa ◽  
Hisanori Ariga
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Glasgow Prognostic Score ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Cox Regression Analysis ◽  
Modified Glasgow Prognostic Score ◽  
Kaplan Meier ◽  
Muscle Invasive

Abstract In patients with various cancers, modified Glasgow prognostic score (mGPS) before treatment has predicted prognoses after antitumor therapy. This study aimed to assess whether pretreatment mGPS also has predictive value in patients with muscle-invasive bladder cancer (MIBC) after radiotherapy. A retrospective review accumulated 98 consecutive MIBC patients treated with definitive 3D-conformal radiotherapy from January 2011 to December 2016 in a single center. It included cT2-4bN0-3M0 patients with a median age of 79 years (range: 49 to 95 years). Radiotherapy was delivered at 60–66 Gy for bladder cancer. Patients were categorized in terms of their pretreatment serum albumin and C-reactive protein (CRP) values as mGPS_0, mGPS_1, and mGPS_2. Among them, cumulative overall survival (OS) rates were compared by Kaplan–Meier plots with log-rank tests. The number of patients with mGPS_0, mGPS_1, and mGPS_2 were 40, 40, and 18, respectively. The median follow-up time for all patients was 19 months (range: 2–73 months). The 2-year OS rate for all patients was 75.7%. The 2-year OS rates for mGPS_0, mGPS_1, and mGPS_2 were 85.1%, 71.3%, and 60.9%, respectively. Kaplan–Meier curves revealed a significantly higher cumulative OS rate for mGPS_0 compared with mGPS_1 and mGPS_2 (P = 0.003). Using multivariate Cox regression analysis, mGPS_0 and good performance status were associated with favorable OS rates, of which mGPS_0 was more significant (Hazard ratio 2.74, 95% CI 1.30–5.57, P = 0.008). Modified Glasgow prognostic score may be a novel biomarker that can predict survival in patients with MIBC after radiotherapy.

scholarly journals Machine learning prediction models based on hub genes related to immune phenotypes in muscle-invasive bladder cancer treated with immune checkpoint blockade

2021 ◽  
Author(s):  
Peiheng Li ◽  
Zhi-Xin Chen ◽  
Dong Wang ◽  
Zhi Zheng ◽  
Zhi-Gang Ji
Keyword(s):  
Bladder Cancer ◽  
Real Time ◽  
Prediction Models ◽  
Prognostic Score ◽  
Invasive Bladder Cancer ◽  
Hub Genes ◽  
Muscle Invasive Bladder Cancer ◽  
Omics Analysis ◽  
Immune Phenotypes ◽  
Muscle Invasive

Abstract Background Bladder cancer is one of the most frequent cancers in the world. Muscle-invasive bladder cancer (MIBC) is the aggressive subtype with higher morbidity and mortality. Immune check point blockade (ICB) therapy has shown its potential for treating MIBC, but is limited due to the lack of predictive biomarkers. Methods 1601 MIBC transcriptomic profiles were obtained from 10 datasets. Unsupervised clustering of immune phenotypes in MIBC was performed based on immune-related signature genes selected by us. We analyzed the characteristics including microenvironments, metabolic pathways, and survival rates in different phenotypes. Multi-omics analysis and WGCNA plus protein-protein interaction (PPI) analysis were performed to identify hub genes of differentially expressed genes (DEGs) distinguishing phenotypes related to prognosis. The hub DEGs were further validated by real-time quantitative PCR (qPCR). A model was established and CART was employed to predict the responses of patients treated with ICB. Results Of various immune phenotypes, cluster 3C was the most “inflamed” subcluster with the best prognosis, while cluster 1A was associated with “non-inflammation” and worst prognosis. There was no intersection of hub DEGs selected by WGCNA plus PPI analysis and multi-omics analysis. WGCNA plus PPI analysis identified 5 hub genes related to the survival rate of patients, IFNG, CXCR6, IL2RB, LCK, and PSMB10. Real-time qPCR results indicated that the expression levels of 5 hub genes were significantly lower in tumors. The 5 hub genes were further utilized for prognostic score model and decision tree analysis. The areas under the curve (AUC) of the ROC curves predicting 5-year endpoint generated from the risk-based prediction model were 0.652. The mean accuracy, sensitivity, and specificity of CART for predicting stable disease/progressive disease were 70.1%, 70.0% and 71.7%. Conclusions The 5 hub genes and generated models showed the potential for predicting the prognosis for patients receiving ICB therapy. The molecular mechanisms regulating the expression of the hub genes require further studies in the future.

scholarly journals Stromal LAG-3+cells infiltration defines poor prognosis subtype muscle-invasive bladder cancer with immunoevasive contexture

2020 ◽  
Vol 8 (1) ◽  
pp. e000651 ◽  
Author(s):  
Han Zeng ◽  
Quan Zhou ◽  
Zewei Wang ◽  
Hongyu Zhang ◽  
Zhaopei Liu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Mrna Level ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

BackgroundLymphocyte activation gene 3 (LAG-3) is a promising immune checkpoint therapeutic target being evaluated in clinical trials. We assessed the LAG-3+cells distribution, its association with clinical outcomes and immune contexture and its role in the landscape of muscle-invasive bladder cancer (MIBC) treatment.Methods141 patients with MIBC from Zhongshan Hospital were included for survival and adjuvant chemotherapy (ACT) benefit analyses. 32 fresh resected samples of MIBC were collected to detect CD8+T cells functional state. The molecular classification analyses were based on 391 patients with MIBC from The Cancer Genome Atlas. Immunohistochemistry and flow cytometry were performed to characterize various immune cells infiltration.ResultsIn Kaplan-Meier analyses and Cox regression models, stromal LAG-3+cells enrichment was consistently associated with inferior overall survival and disease-free survival, and indicated suboptimal responsiveness to ACT. Patents with high stromal LAG-3+cells possessed increased protumor cells, immunosuppressive cytokines and immune checkpoint expression. The phenotypic analyses of CD8+T cells correlated its dysfunctional state with LAG-3+cells. Besides, LAG-3 mRNA level was linked to luminal and basal subtypes of MIBC. LAG-3-high tumors exhibited limited FGFR3 mutation and signaling signature, and displayed activated immunotherapeutic and EGFR-associated pathway.ConclusionsStromal LAG-3+cells abundance indicated an immunoevasive contexture with dysfunctional CD8+T cells, and represented an independent predictor for adverse survival outcome and ACT resistance in MIBC. LAG-3 expression could potentially be a novel biomarker for FGFR3-targeted and EGFR-targeted therapies and immunotherapy. The crucial role of LAG-3+cells in the therapeutic landscape of MIBC needs further validation retrospectively and prospectively.

scholarly journals Chemoradiotherapy in octogenarians as primary treatment for muscle-invasive bladder cancer

2017 ◽  
Vol 11 (1-2) ◽  
pp. 24 ◽  
Author(s):  
Victor A. McPherson ◽  
George Rodrigues ◽  
Glenn Bauman ◽  
Eric Winquist ◽  
Joseph Chin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Local Recurrence ◽  
Cox Regression ◽  
Bladder Tumour ◽  
Invasive Bladder Cancer ◽  
High Dose ◽  
Muscle Invasive Bladder Cancer ◽  
Trimodality Therapy ◽  
Muscle Invasive ◽  
Salvage Cystectomy

Introduction: While radical cystectomy is the gold standard for muscle-invasive bladder cancer (MIBC), in octogenarians cystectomy results in a higher perioperative mortality rate (6.8‒11.1%) than in younger patients (2.2%). Trimodality therapy is a bladdersparing regimen composed of transurethral resection of bladder tumour (TURBT) and chemoradiotherapy, with intent for salvage cystectomy, and has a 62.5‒90% initial complete response rate. In this study, we evaluate TURBT and chemoradiotherapy without salvage cystectomy in medically inoperable octogenarian patients.Methods: We identified a retrospective cohort of patients aged 80‒89 years with invasive urothelial carcinoma who received combination chemoradiotherapy between 2008 and June 2014. Outcomes were evaluated by Kaplan-Meier (KM) and Cox regression.Results: In 40 patients, the mean age was 84.5 years (interquartile range [IQR] 83‒86). Seventeen patients received hypofractionated, low-dose radiotherapy (LD) (37.5‒40 Gy), while 23 received conventionally fractionated radiotherapy (high-dose [HD]) (50‒65 Gy). Mean overall survival (OS) was 20.7 months (IQR 12.75‒23.25), while mean recurrence-free survival (RFS) was 13.75 months (IQR 3.75‒16.5). Patients receiving HD radiotherapy showed improved OS and local RFS (LRFS) without significant differences in Grade 3‒4 toxicities. Univariate Cox regression identified hydronephrosis as a predictor of worse OS and local recurrence and HD radiotherapy as a predictor of improved OS and local recurrence rates. Multivariate Cox regression identified hydronephrosis to be a significant predictor of LRFS.Conclusions: Primary chemoradiotherapy for inoperable patients with MIBC resulted in a three-year OS of 54.9% (comparable to cystectomy) and three-year RFS of 42.3%. Superior outcomes were associated with more aggressive chemoradiotherapy treatment. The results of the local control subanalyses in this study are hypothesisgenerating due to the limited patient numbers in the cohort.

scholarly journals Post-Bacille Calmette–Guerin surveillance for non-muscle invasive bladder cancer: do random biopsies offer an advantage?

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Nassib Abou Heidar ◽  
Muhieddine Saadeddine Labban ◽  
Alexandre Khalil Armache ◽  
Muhammad Ahmad Bulbul ◽  
Albert Elias El-Hajj ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Carcinoma In Situ ◽  
Cox Regression ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Flexible Cystoscopy ◽  
Time To Recurrence ◽  
Surveillance Method ◽  
Muscle Invasive

Abstract Background The optimal surveillance method for recurrence of non-muscle invasive bladder cancer (NMIBC) after intravesical BCG treatment is unknown. The aim of this study is to assess the difference between two surveillance methods: cystoscopy with bladder biopsies and office-based flexible cystoscopy in detecting NMIBC recurrence and time to recurrence. Methods Charts of patients who underwent transurethral resection of bladder tumor with subsequent intravesical Bacillus Calmette–Guerin (BCG) treatment were reviewed between January 2015 and December 2018. Baseline demographics and oncological parameters were compared between the two methods of surveillance. Then, the role of the surveillance method for NMIBC recurrence and time to recurrence were evaluated in backward logistic regression and hazard ratios estimated in Cox regression models, respectively. Results Fifty-one patients (50.5%) underwent office-based flexible cystoscopy and 50 patients (49.5%) had bladder biopsies. The patients undergoing either surveillance methods were comparable for baseline demographic and oncological parameter. The predictors of recurrence and earlier BCG relapse were increased body mass index, the presence of multifocal tumors, the presence of concurrent carcinoma in situ, and tumor size at presentation. Bladder cancer recurrence was mostly affected by multifocality of the disease [OR 3.61 95%CI (1.17–11.15)] and the presence of concomitant carcinoma in situ [4.35 (1.29–14.68)]. Yet, the surveillance method neither predicted a higher recurrence yield nor earlier diagnosis. Conclusion In our cohort, there is neither difference in recurrence yield nor earlier diagnosis of recurrence between office-based flexible cystoscopy and bladder biopsies. Larger prospective studies are needed to assess the generalizability of these findings.

scholarly journals Predictive value of prognostic nutritional index and systemic immune‐inflammation index on tumor progression in bladder cancer patients with after radical cystectomy

2020 ◽  
Author(s):  
Jiatong Zhou ◽  
Xitong Xu ◽  
RanLu Liu
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Predictive Value ◽  
Cox Regression ◽  
Prognostic Nutritional Index ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Nutritional Index ◽  
Immune Inflammation ◽  
Muscle Invasive

Abstract OBJECTIVES: The purpose of this study was to explore the predictive value of preoperative prognostic nutritional index(PNI) and systemic immune‐inflammation index(SII) for local tumor stage in bladder cancer(BC) after radical cystectomy(RC).METHODS: We researched our database between April 2011 and October 2019. There were 195 BC patients who underwent RC. The PNI and SII were calculated using preoperative blood sample results. The predictive value of SII and PNI was analysed with univariate and multivariate Cox regression models. Receiver operating characteristic (ROC) was used to determine the optimum PNI. Signifcant P was P<0.05.RESULTS: Of patients, all patients were males with a mean age of 67.94±8.97years. Mean serum albumin was 42.13±4.28(g/L), mean PNI score was 51.29±6.09 and mean SII was 661.67±506.22. Multivariable Cox regression analysis demonstrated that PNI scores and SII could not play a significantly predictive factor between muscle invasive bladder cancer(MIBC) and non-muscle-invasive bladder cancer(NMIBC). While we also found PNI was an independent risk factors for predicting tumor stagep(pT＜3a and pT≥3a).CONCLUSIONS: Our research revealed that preoperative low PNI but not SII could be used as an independent factor to predict worse pathologically stage(pT≥3a). But preoperative PNI and SII might not were significantly related with the incidence risk of muscle invasive. We still need future studies with large cohorts to identify our results.

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