Dataset Information

Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer.

ABSTRACT: Bladder cancer is one of the most common malignant tumors of the urinary system that seriously threatens the health of a population. In recent years, the application of immunotherapy has significantly changed the treatment of bladder cancer, but only some patients can benefit from the treatment with immune-checkpoint inhibitors. Many problems are unsolved in the field of bladder cancer immunotherapy, especially in the search for genes that are critical to the level of immune cell infiltration and new effective therapeutic targets. We attempted to use bioinformatics analysis to identify immune gene markers related to the prognosis of bladder cancer and to establish a prognostic signature for bladder cancer patients based on their immune gene expression profiles. We used univariate Cox proportional hazards regression analysis, the least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox proportional hazards regression analysis from The Cancer Genome Atlas bladder cancer cohort (TCGA-BLCA). Fifteen genes related to prognosis were screened using the survival analysis, correlation analysis, cancer and adjacent cancer differential expression analysis, and mutation analysis. The potential biological role of these genes was determined using survival analysis and principal component analysis (PCA). The receiver operating characteristic (ROC) curve assesses the prognostic value of the predictive signature. The gene ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG), Gene set enrichment analysis (GSEA), and other methods were used to reveal the differential gene enrichment in the signaling pathways and cellular processes of high- and low-risk groups. The single-sample GSEA (ssGSEA) method was used to quantify the infiltration levels of 24 immune cells in the tumor immune microenvironment and these immune genes were found to be closely related to the tumor immune microenvironment. In summary, we screened 15 immune genes that were closely related to bladder cancer overall survival (OS) and may be potential prognostic indicators of bladder cancer. They may have research and clinical application value in bladder cancer immunotherapy. We used 15 immune genes to construct a new immune-related gene signature that was verified and could be helpful in improving individualized prognosis of patients with bladder cancer.

SUBMITTER: Chen X

PROVIDER: S-EPMC7324668 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer.

Chen Xingyu X Jin Yi Y Gong Lian L He Dong D Cheng YaXing Y Xiao Mengqing M Zhu Yuxing Y Wang Zhanwang Z Cao Ke K

Frontiers in genetics 20200623

Bladder cancer is one of the most common malignant tumors of the urinary system that seriously threatens the health of a population. In recent years, the application of immunotherapy has significantly changed the treatment of bladder cancer, but only some patients can benefit from the treatment with immune-checkpoint inhibitors. Many problems are unsolved in the field of bladder cancer immunotherapy, especially in the search for genes that are critical to the level of immune cell infiltration an ...[more]

PMID: 32655621

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Project description:Background: Immune checkpoint inhibitor therapy has changed the treatment model of metastatic bladder cancer. However, only approximately 20% of patients benefit from this therapy, and robust biomarkers to predict the effect of immunotherapy are still lacking. In this study, we aimed to investigate whether immune-related genes could be indicators for the prognosis of bladder cancer patients and the effect of immunotherapy. Methods: Based on bladder cancer dataset from the Cancer Genome Atlas (TCGA) and GSE48075, 22 immune microenvironment-related cells were identified by CIBERSORT. After performing a series of bioinformatic and machine learning approaches, we identified distinct tumor microenvironment clusters and three bladder cancer specific immune-related genes (EGFR, OAS1 and MST1R). Then, we constructed immune-related gene risk score (IRGRS) by using the Cox regression method and validated it with the IMvigor210 dataset. Results: IRGRS-high patients had a worse overall survival than IRGRS-low patients, which was consistent with the result in the IMvigor210 dataset. Comprehensive analysis shows that patients with high IRGRS scores are mainly enriched in basal/squamous type (Ba/Sq), and tumor metabolism-related pathways are more Active, with higher TP53 and RB1 gene mutation rates, lower CD4+/CD8+ T cell infiltration, higher M0 macrophage infiltration, and lower immunotherapy efficacy. In contrast, Patients with low IRGRS scores are mainly enriched in the luminal papillary type (LumP), which is associated with the activation of IL-17 and TNF signaling pathways, higher mutation rates of FGFR3 and CDKN1A genes, higher CD4+/CD8+ T cell infiltration content, and The level of M0 macrophage infiltration was relatively low, and the immunotherapy was more probably effective. Conclusion: Our study constructed an IRGRS for bladder cancer and clarified the immune and molecular characteristics of IRGRS-defined subgroups of bladder cancer to investigate the association between IRGRS and its potential implications for prognosis and immunotherapy.

Project description:Background: A new form of cell death, copper-dependent cell death (termed cuproptosis), was illustrated in a recent scientific study. However, the biological function or prognostic value of cuproptosis regulators in bladder cancer (BLCA) remains unknown. Materials and Methods: Sequencing data obtained from BLCA samples in TCGA and GEO databases were preprocessed for analysis. Biological function and immune cell infiltration levels evaluated by gene set variation analysis (GSVA) were employed to calculate enrichment scores. Iteration least absolute shrinkage and selection operator (LASSO) and COX regression model were employed to select feature genes and construct a novel cuproptosis-related (CR) score signature. The genomics of drug sensitivity in cancer (GDSC) and tumor immune dysfunction and exclusion (TIDE) analysis were used to predict the chemotherapy and immunotherapy efficacy for BLCA patients. The relative expression of the genes involved in the signature was also verified by real-time quantitative PCR (qRT-PCR) in cell lines and tissues. Results: Expression abundance and the prognostic value of cuproptosis regulators proved that cuproptosis might play a vital part in the carcinogenesis of BLCA. GSVA revealed that cuproptosis regulators might be associated with metabolism and metastasis-related pathways such as TGF-β, protein secretion, oxidative Phosphorylation, MYC targets, MTORC1, and adipogenesis pathways. CR scores could predict the prognosis and evaluate the chemotherapy and immunotherapy efficacies of BLCA. CR scores were positively correlated with EMT, MYC, MTORC1, HEDGEHOG, and E2F signaling pathways; meanwhile, they were negatively correlated with several immune cell infiltration levels such as CD8+ T cells, γδT cells, and activated dendritic cells. Several GEO datasets were used to validate the power of prognostic prediction, and a nomogram was also established for clinical use. The expressions of DDX10, RBM34, and RPL17 were significantly higher in BLCA cell lines and tissues in comparison with those in the corresponding normal controls. Conclusion: Cuproptosis might play an essential role in the progression of BLCA. CR scores could be helpful in the investigation of prognostic prediction and therapeutic efficacy and could make contributions to further studies in BLCA.

Dataset Information

Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer.

Publications

Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer.

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