scholarly journals Low T-cell Receptor Diversity, High Somatic Mutation Burden, and High Neoantigen Load as Predictors of Clinical Outcome in Muscle-invasive Bladder Cancer

2016 ◽  
Vol 2 (4) ◽  
pp. 445-452 ◽  
Author(s):  
Noura J. Choudhury ◽  
Kazuma Kiyotani ◽  
Kai Lee Yap ◽  
Alexa Campanile ◽  
Tatjana Antic ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cell ◽  
Clinical Outcome ◽  
T Cell Receptor ◽  
Somatic Mutation ◽  
Cell Receptor ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Mutation Burden ◽  
Muscle Invasive

scholarly journals A stemness-related seven-gene signature for predicting prognosis and treatment response in muscle invasive bladder cancer

2020 ◽  
Author(s):  
Maolang Tian ◽  
Jinlan He ◽  
Jiaqi Han ◽  
Hong Zhu
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Clinical Outcome ◽  
Treatment Response ◽  
Risk Score ◽  
Gene Signature ◽  
Invasive Bladder Cancer ◽  
Cancer Stemness ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Abstract Background: Muscle invasive bladder cancer (MIBC) is an aggressive cancer characterized by therapeutic resistance and poor prognosis, which are possibly due to the existence of cancer stem cells (CSCs). In this study, we aimed to characterize the expression of cancer stemness-related genes and develop a multi-gene risk signature to predict clinical outcome and treatment response in MIBC.Methods: The mRNA expression data and clinical data of MIBC patients were collected from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, which included the TCGA training cohort (n = 333) and three GEO validation cohorts, GSE13507 (n = 165), GSE32548 (n = 127), and GSE48075 (n = 72). A list of 166 stemness-related genes were obtained from the Cancer Single Cell State Atlas (CancerSEA) database and prognostic genes for overall survival (OS) were identified by univariate Cox analysis. Then, the least absolute shrinkage and selection operator (LASSO) regression and stepwise multivariate Cox regression were performed to generate a multi-gene risk signature. Kaplan-Meier curve, time-dependent receiver operating characteristic (ROC) curve, multivariate analysis, and stratification analysis were used to evaluate the performance of the gene signature. We also explored the relationship between risk score and response to chemotherapy and radiotherapy in MIBC patients. Moreover, independent prognostic factors for OS were combined together into a nomogram to improve predictive performance.Results: Firstly, a total of 25 prognostic genes were identified. Then, a seven-gene risk signature (EGFR, FOXA2, HES1, MME, RBM6, SMOC2, and TFRC) was constructed and it could robustly classify MIBC patients into high -risk and low-risk groups with different clinical outcomes. ROC curves showed that the seven-gene signature had a robust predictive accuracy in four cohorts. Besides, high risk score was significantly associated with advanced clinical stage and treatment failure. As an independent risk factor for OS, the stemness-related seven-gene signature could achieve better prognostic accuracy when integrated with clinical factors. Conclusions: We developed and validated a robust stemness-related gene signature which could robustly predicate clinical outcome and shed light on the cancer stemness in bladder cancer.

scholarly journals Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer

2020 ◽  
Vol 8 (2) ◽  
pp. e000978
Author(s):  
Zhaopei Liu ◽  
Quan Zhou ◽  
Zewei Wang ◽  
Hongyu Zhang ◽  
Han Zeng ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
T Cell ◽  
Invasive Bladder Cancer ◽  
Th2 Cells ◽  
Cancer Center ◽  
Muscle Invasive Bladder Cancer ◽  
Cell Abundance ◽  
Immune Contexture ◽  
Muscle Invasive

BackgroundT-cell immunoglobulin and ITIM domain (TIGIT) is identified as a novel checkpoint receptor that can facilitate immune escape via mediating T-cell exhaustion in tumors. However, the clinical significance and immune contexture correlation of intratumoral TIGIT+ CD8+ T-cells remain to be further explored in muscle-invasive bladder cancer (MIBC).Methods259 patients with MIBC from two clinical centers (Zhongshan Hospital, n=141; Shanghai Cancer Center, n=118) were analyzed to evaluate the prognostic value and immune contexture association of TIGIT+ CD8+ T-cells through immunohistochemistry. Fresh tumor tissue samples from 26 patients with MIBC were examined to discover the phenotype of this CD8 subpopulation by flow cytometry.ResultsHigh infiltration of intratumoral TIGIT+ CD8+ T-cells predicted poor overall survival (OS) and recurrence-free survival (RFS) in MIBC. For patients with stage II MIBC with low infiltration of TIGIT+ CD8+ cells, adjuvant chemotherapy (ACT) could significantly prolong their OS and RFS. Intratumoral TIGIT+ CD8+ T-cell abundance was correlated with impaired CD8+ T-cell cytotoxicity and exhibited production of immunosuppressive cytokine IL-10. Further analysis of tumor-infiltrating immune cell landscape revealed TIGIT+ CD8+ T-cells were associated with suppressive immune contexture, including Th2 cells, regulatory T-cells, mast cells and neutrophils.ConclusionIntratumoral TIGIT+ CD8+ T-cell abundance could serve as an independent prognosticator for clinical outcome and a predictive biomarker for inferior ACT responsiveness. Intratumoral TIGIT+ CD8+ T-cell abundance correlated with dampened CD8+ T-cell antitumor immunity and immunosuppressive contexture abundance, highlighting a tumor-promoting role of TIGIT+ CD8+ T-cells.

scholarly journals The effect of smoking and timing of smoking cessation on clinical outcome in non–muscle-invasive bladder cancer

2015 ◽  
Vol 33 (2) ◽  
pp. 65.e9-65.e17 ◽  
Author(s):  
Anne J. Grotenhuis ◽  
Cornelis W. Ebben ◽  
Katja K. Aben ◽  
J. Alfred Witjes ◽  
Alina Vrieling ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Smoking Cessation ◽  
Clinical Outcome ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

scholarly journals Prognostic Factors of Non-Muscle Invasive Bladder Cancer: A Study Based on Next-generation Sequencing

2020 ◽  
Author(s):  
Yanxiang Shao ◽  
Xu Hu ◽  
Zhen Yang ◽  
Thongher Lia ◽  
Weixiao Yang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Factors ◽  
Next Generation Sequencing ◽  
Invasive Bladder Cancer ◽  
Next Generation ◽  
Muscle Invasive Bladder Cancer ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Muscle Invasive ◽  
Generation Sequencing

Abstract ObjectiveTo investigate the genetic prognostic factors for the recurrence of non-muscle invasive bladder cancer. Materials and MethodsThe patients underwent transurethral resection of bladder tumor and received bacillus Calmette–Guérin (BCG) or epirubicin. Next-generation sequencing was performed and alterations of genes, pathways, and tumor mutation burden were recorded. Associations between these clinicopathological and genetic variants were estimated, and prognostic factor identified.ResultsA total of 58 cases were included in our study, and 46 patients underwent treatment with BCG. FGFR3 was the most frequently altered gene (48%), and more commonly detected in intermediate-risk patients. Univariate Cox analysis demonstrated that 10 genes were significantly correlated with BCG failure, while NEB, FGFR1 and SDHC were independent recurrence predictors. Besides, epigenetic-related gene pathway mutations were negatively correlated with recurrence (hazard ratio: 0.198, P=0.023). DNA damage response and repair gene alterations were positively correlated with tumor burden, while altered TP53 was most frequent among these genes and significant correlated with high tumor burden.ConclusionBCG instillation significantly reduced the rate of recurrence compared with epirubicin in this population. Potential biomarkers and therapeutic targets were found with the help of next-generation sequencing; correlations between DDR genes alterations and high tumor mutation burden were also demonstrated.

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