An immune relevant signature for predicting prognoses and immunotherapeutic responses in patients with muscle‐invasive bladder cancer (MIBC)

Jiang, Wen; Zhu, Dandan; Wang, Chenghe; Zhu, Yu

doi:10.1002/cam4.2942

Cited by 60 publications

(54 citation statements)

References 59 publications

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“…A recent study 13 has constructed a ceRNA network, which was of high prognostic value, to achieve a deeper comprehension to the RNA regulatory network in BLCA. Besides, although several immune-relevant signature [34][35][36] have been constructed to predict the survival of BLCA, few studies concentrated on immune-relevant genes revealing the prognosis based on ceRNA hypothesis. In this study, we integrated the TCGA-BLCA database and GEO database to determine an immune-related risk signature and constructed an immune-relevant ceRNA network including 5 mRNAs, 24 miRNAs and 86 lncRNAs, leading to a better understanding of the oncological immunology of BLCA from the angle of RNA interactions.…”

Section: Discussionmentioning

confidence: 99%

“…Utilizing ssGSEA strategy, which has been proved to be effective for tumor grouping based on immune in ltrating status in multiple studies 17,35,37 , 411 BLCA patients were labeled with high-immunein ltrating and low-immune-in ltrating, and then genomic difference detection was performed to achieve the latent immune-relevant lncRNA, mRNA and miRNA. To identify the genes correlated with tumorigenesis of BLCA, we compared the genomic expression difference between the parcancerous tissues and malignant bladder tissues by "edgeR" package of R. WGCNA was implemented to obtain the lncRNAs mostly relevant to the process of immune response.…”

Section: Discussionmentioning

confidence: 99%

“…By means of immune grouping and correlation test, we ensure the risk score is closely correlated with tumor immunity. Compared with other immune-related risk models [34][35][36] , we rstly made use of ceRNA hypothesis to establish a prognostic signature in order to make sure the risk score was immune-related. The analysis results of functional annotation indicated that the immune-related pathways, such as complement and in ammatory response, were signi cantly enriched in the high-risk group, which once again veri ed the immunological correlation of risk score.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Construction of An Immune-Related CeRNA Network as a Prognostic Signature in Bladder Cancer

Zhou¹,

Tian²,

Yang³

et al. 2020

Preprint

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Background: Immunotherapy has been proved to be effective for bladder cancer (BLCA). However, the molecular network involved in BLCA tumor immune response remains unclear. This study aims to construct an immune-related ceRNA network and to identify the prognostic value. Methods: Based on The Cancer Genome Atlas (TCGA), we used single-sample gene set enrichment analysis (ssGSEA), weighted gene co-expression network analysis (WGCNA) to determine immune-related mRNA, lncRNA and miRNA. Then least absolute shrinkage, and selection operator (LASSO) and Cox regression were performed to identify the mRNAs with high prognostic value, and accordingly, the risk score was calculated. Internal and external validation were performed both in TCGA and GSE13507 with Kaplan-Meier (KM) survival and Receiver Operating Characteristic (ROC) curve analysis. Using the immune-related mRNA, lncRNA and miRNA, a ceRNA network was established via MiRcode, starBase, miRDB, miRTarBase and TargetScan. Besides, we also explore the relationship between the risk score and immune cell infiltration via CIBERSORT algorithm. Results: 5 mRNAs (PCGF3, FASN, DPYSL2, TGFBI and NTF3) were ultimately identified, and KM survival analysis displayed the 5-mRNA risk signature could predict the prognosis of BLCA with high efficacy both in TCGA (p = 1.006e-13) and GSE13507 (p = 7.759e-04). Using miRNA targeting molecular prediction database, an immune-related ceRNA network, including 5 mRNAs, 24 miRNAs and 86 lncRNAs, was constructed. Memory B cells, activated dendritic cells, and regulatory T cells infiltration into tumors were negatively correlated with risk score, while the infiltration levels of macrophages M0, M1 and M2 were positively correlated with risk score. Conclusion: This study helped to better understand the molecular mechanisms of tumor immune response from the view of ceRNA hypothesis, and provided a novel prognostic signature for bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Construction of An Immune-Related CeRNA Network as a Prognostic Signature in Bladder Cancer

Zhou¹,

Tian²,

Yang³

et al. 2020

Preprint

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“…Studies demonstrated that immune-related lncRNAs have a unique value in the prognosis of several cancers. The heterogeneous expression of lncRNAs was identi ed among different immune-in ltrating groups in muscle-invasive bladder cancer [10]. The potential value of immune-related lncRNAs as prognostic indicators has been validated in several cancers.…”

Section: Introductionmentioning

confidence: 99%

Development and verification of immune-related long non-coding RNA prognostic signature in bladder cancer

Lai¹,

Wu²,

Li³

et al. 2020

Preprint

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Background: Bladder cancer is the second most common malignant tumor in urogenital system. The research aimed to investigate the prognostic role of immune-related long non-coding RNA (lncRNA) in bladder cancer. Methods: We extracted 411 bladder cancer samples from The Cancer Genome Atlas database. Single-sample gene set enrichment analysis was employed to assess the immune cell infiltration of these samples. We recognized differentially expressed lncRNAs between tumors and paracancerous tissues, and differentially expressed lncRNAs between the high and low immune cell infiltration groups. Venn diagram analysis detected differentially expressed lncRNAs that intersected the above groups. LncRNAs with prognostic significance were identified by regression analysis and survival analysis. Multivariate Cox analysis was used to establish the risk score model. The nomogram was established and evaluated by receiver operating characteristic (ROC) curve analysis, concordance index (C-index) analysis, calibration chart, and decision curve analysis (DCA). Additionally, we performed gene set enrichment analysis to explore the potential functions of the screened lncRNAs in tumor pathogenesis.Results: Three hundred and twenty differentially expressed lncRNAs were recognized. We randomly divided patients into the training data set and the testing data set at a 2: 1 ratio. In the training data set, 9 immune-related lncRNAs with prognostic significance were identified. The risk score model was constructed to classify patients as high- and low-risk cohorts. Patients in the low-risk cohort had better survival outcomes than those in the high-risk cohort. The nomogram was established based on the indicators including age, gender, TNM stage, and risk score. The model’s predictive performance was confirmed by ROC curve analysis, C-index analysis, calibration chart, and DCA. The testing data set also achieved similar results. Bioinformatics analysis suggested that the 9-lncRNA signature was involved in modulation of various immune responses, antigen processing and presentation, and T cell receptor signaling pathway.Conclusions: The immune-related lncRNAs have the potential to predict the prognosis of bladder cancer and may play a key role in bladder cancer biology.Trial registration: It was a retrospective study and the gene expression data were obtained from the TCGA database. Trial registration was not needed.

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“…Cao et al developed a seven-gene signature related with epithelial-mesenchymal transition (EMT) process, which could stratify patients into different risk groups with distinct prognosis[17]. Jiang et al analyzed genes associated with immune cells infiltration in MIBC and developed a nine-gene signature which could distinguish patients with different prognoses and immunotherapeutic response[18]. However, genetic biomarkers associated with cancer stemness features were seldom studied in bladder cancer.In the present study, we developed and validated a novel stemness-related seven-gene signature for predicting prognosis and treatment response in MIBC patients, which is different from previously reported gene signatures.…”

mentioning

confidence: 99%

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

Tian¹,

He²,

Han³

et al. 2020

Preprint

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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.

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An immune relevant signature for predicting prognoses and immunotherapeutic responses in patients with muscle‐invasive bladder cancer (MIBC)

Cited by 60 publications

References 59 publications

Construction of An Immune-Related CeRNA Network as a Prognostic Signature in Bladder Cancer

Construction of An Immune-Related CeRNA Network as a Prognostic Signature in Bladder Cancer

Development and verification of immune-related long non-coding RNA prognostic signature in bladder cancer

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

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