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:This study aimed to identify the genetic signatures associated with disease prognosis in bladder cancer. We used 165 primary bladder cancer samples, 23 recurrent non-muscle invasive tumor tissues, 58 normal looking bladder mucosae surrounding cancer and 10 normal bladder mucosae for microarray analysis. Hierarchical clustering was used to stratify the prognosis-related gene classifiers. For validation, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) of top-ranked 14 genes was performed. On unsupervised hierarchical clustering using prognosis related gene-classifier, tumors were divided into 2 groups. The high risk gene signatures had significantly poor prognosis compared to low risk gene signatures (P<0.001 by the log-rank test, respectively). The prognosis-related gene classifiers correlated significantly with recurrence of non-muscle invasive bladder cancer (hazard ratio, 4.09; 95% confidence interval [CI], 1.94 to 8.64; P<0.001), and progression (hazard ratio, 23.68; 95% confidence interval [CI], 4.91 to 114.30; P<0.001), cancer-specific survival (hazard ratio, 29.25; 95% confidence interval [CI], 3.47 to 246.98; P=0.002) and overall survival (hazard ratio, 23.33; 95% confidence interval [CI], 4.97 to 109.50; P<0.001) of muscle invasive bladder cancer (p < 0.001, respectively). No patient with non-muscle invasive bladder cancer experienced cancer progression in low risk gene signature group. Prognosis-related gene classifiers validated by RT- PCR showed identical results. Prognosis related gene-classifiers provided strong predictive value for disease outcome. These gene classifiers could assist in selecting patients who might benefit from more aggressive therapeutic intervention or surveillance. Keywords: Gene expression, Bladder cancer, Prognosis 165 primary bladder cancer samples and 23 recurrent non-muscle invasive tumor tissues from 14 patients were taken in the Chungbuk National University Hospital. Only histologically verified transitional cell carcinoma samples were selected. Simultaneously 58 normal looking bladder mucosae surrounding cancer were obtained during the operation, which were histologically confirmed normal. Also, 10 normal bladder mucosae were obtained from patients with benign disease. The normal controls were determined to be free of cancer after revealing no malignant cells on urine cytology and no observable bladder cancer on cystoscopic examination during operation for their diseases, and were histologically reconfirmed normal.

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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