Development and validation of a molecular prognostic index of bladder cancer based on immunogenomic landscape analysis

Xu, Ning; Ke, Zhi‐Bin; Lin, Xiaodan; Chen, Ye‐Hui; Wu, Yupeng; Chen, Yu; Dong, Ru‐Nan; Chen, Shao‐Hao; Wei, Yong; Zheng, Qing‐Shui; Lin, Yunzhi; Xue, Xue-Yi

doi:10.1186/s12935-020-01343-3

Cited by 20 publications

(19 citation statements)

References 36 publications

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“…There were various components in the tumor microenvironment including tumor cells, immune cells, stromal cells, and extracellular matrix [22]. The ESTIMATE algorithm, which was developed by Yoshihara et al, was recently widely used for exploring tumor microenvironment components [22][23][24]. We calculated stromal score, immune score, ESTI-MATE score, and tumor purity of COAD tumor microenvironment using the ESTIMATE algorithm.…”

Section: Relationships Between Stemness Indices and Tumormentioning

confidence: 99%

A Novel Cancer Stemness-Related Signature for Predicting Prognosis in Patients with Colon Adenocarcinoma

Wang

Ren

et al. 2021

Stem Cells International

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Objective. To explore the cancer stemness features and develop a novel cancer stemness-related prognostic signature for colon adenocarcinoma (COAD). Methods. We downloaded the mRNA expression data and clinical data of COAD from TCGA database and GEO database. Stemness index, mRNAsi, was utilized to investigate cancer stemness features. Weighted gene coexpression network analysis (WGCNA) was used to identify cancer stemness-related genes. Univariate and multivariate Cox regression analyses were applied to construct a prognostic risk cancer stemness-related signature. We then performed internal and external validation. The relationship between cancer stemness and COAD immune microenvironment was investigated. Results. COAD patients with higher mRNAsi score or EREG-mRNAsi score have significant longer overall survival (OS). We identified 483 differently expressed genes (DEGs) between the high and low mRNAsi score groups. We developed a cancer stemness-related signature using fifteen genes (including RAB31, COL6A3, COL5A2, CCDC80, ADAM12, VGLL3, ECM2, POSTN, DPYSL3, PCDH7, CRISPLD2, COLEC12, NRP2, ISLR, and CCDC8) for prognosis prediction of COAD. Low-risk score was associated with significantly preferable OS in comparison with high-risk score, and the area under the ROC curve (AUC) for OS prediction was 0.705. The prognostic signature was an independent predictor for OS of COAD. Macrophages, mast cells, and T helper cells were the vital infiltration immune cells, and APC costimulation and type II IFN response were the vital immune pathways in COAD. Conclusions. We developed and validated a novel cancer stemness-related prognostic signature for COAD, which would contribute to understanding of molecular mechanism in COAD.

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Section: Relationships Between Stemness Indices and Tumormentioning

confidence: 99%

A Novel Cancer Stemness-Related Signature for Predicting Prognosis in Patients with Colon Adenocarcinoma

Wang

Ren

et al. 2021

Stem Cells International

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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%

“…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%

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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“…The transcriptome and clinical data of BCa were obtained from TCGA database (https://portal.gdc.cancer.gov), including 414 BCa cases and 19 normal cases [14]. The clinical features of BCa patients included age, gender, grade, T stage, N stage, M stage, and AJCC stage.…”

Section: Data Acquisitionmentioning

confidence: 99%

Ubiquitination-Related Molecular Subtypes and a Novel Prognostic Index for Bladder Cancer Patients

Cai¹,

Chen²,

Huang³

et al. 2021

Pathol. Oncol. Res.

Self Cite

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Objective: To develop and validate ubiquitination-related molecular subtypes and a novel prognostic index using ubiquitination-related genes (URGs) for patients with bladder cancer (BCa).Materials and Methods: We downloaded the clinical data and transcriptome data of BCa from TCGA and GEO database. Consensus clustering analysis was conducted to identify ubiquitination-related molecular subtypes for BCa. Besides, we performed univariate and multivariate Cox regression analysis to develop a novel prognostic URGs-related index for BCa. We conducted internal and external verification in TCGA cohort and GEO cohort, respectively. Furthermore, the associations of ubiquitination-related molecular subtypes and prognostic index with tumor immune environment were also investigated.Results: A total of four ubiquitination-related molecular subtypes of BCa were finally identified. These four molecular subtypes had significantly different clinical characteristics, prognosis, PD-L1 expression level and tumor microenvironment. Besides, we developed a novel prognostic index using six URGs (including HLA-A, TMEM129, UBE2D1, UBE2N, UBE2T and USP5). The difference in OS between high and low-risk group was statistically significant in training cohort, testing cohort, and validating cohort. The area under ROC curve (AUC) for OS prediction was 0.736, 0.723, and 0.683 in training cohort, testing cohort, and validating cohort, respectively. Multivariate survival analysis showed that this index was an independent predictor for OS. This prognostic index was especially suitable for subtype 1 and 3, older, male, high grade, AJCC stage III-IV, stage N0, stage T3-4 BCa patients.Conclusions: This study identified a total of four ubiquitination-related molecular subtypes with significantly different tumor microenvironment, prognosis, clinical characteristics and PD-L1 expression level. Besides, a novel ubiquitination-related prognostic index for BCa patients was developed and successfully verified, which performed well in predicting prognosis of BCa.

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Development and validation of a molecular prognostic index of bladder cancer based on immunogenomic landscape analysis

Cited by 20 publications

References 36 publications

A Novel Cancer Stemness-Related Signature for Predicting Prognosis in Patients with Colon Adenocarcinoma

A Novel Cancer Stemness-Related Signature for Predicting Prognosis in Patients with Colon Adenocarcinoma

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

Ubiquitination-Related Molecular Subtypes and a Novel Prognostic Index for Bladder Cancer Patients

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