Dataset Information

Prognostic value of DNA repair genes based on stratification of glioblastomas.

ABSTRACT: Abnormal expression of DNA repair genes is frequently associated with cancerogenesis of many tumors, however, the role DNA repair genes play in the progression of glioblastoma remains unclear. In this study, taking advantage of large scale of RNA-seq data, as well as clinical data, the function and prognosis value of key DNA repair genes in glioblastoma were analyzed by systematically bioinformatic approaches. Clustering was performed to screen potentially abnormal DNA repair genes related to the prognosis of glioblastoma, followed by unsupervised clustering to identify molecular subtypes of glioblastomas. Characteristics and prognosis differences were analyzed among these molecular subtypes, and modular driver genes in molecular subtypes were identified based on changes in expression correlation. Multifactor Cox proportional hazard analysis was used to find the independent prognostic factor. A total of 15 key genes, which were significantly related to prognosis, were identified and four molecular subtypes of disease were obtained through unsupervised clustering, based on these 15 genes. By analyzing the clinical features of these 4 molecular subtypes, Cluster 4 was found to be different from others in terms of age and prognosis level. A total of 5 key DNA repair genes, CDK7, DDB2, RNH1, RFC2 and FAH, were screened to be significantly related to the prognosis of glioblastomas (p = 9.74e-05). In summary, the DNA repair genes which can predict the prognosis of patients with Glioblastoma multiforme (GBM) were identified and validated. The expression level of DNA repair genes shows the potential of predicting the prognosis and therapy design in targeting GBM.

SUBMITTER: Kun S

PROVIDER: S-EPMC5601646 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Prognostic value of DNA repair genes based on stratification of glioblastomas.

Kun Sun S Duan Qiwen Q Liu Gang G Lu Jing-Min JM

Oncotarget 20170427 35

Abnormal expression of DNA repair genes is frequently associated with cancerogenesis of many tumors, however, the role DNA repair genes play in the progression of glioblastoma remains unclear. In this study, taking advantage of large scale of RNA-seq data, as well as clinical data, the function and prognosis value of key DNA repair genes in glioblastoma were analyzed by systematically bioinformatic approaches. Clustering was performed to screen potentially abnormal DNA repair genes related to th ...[more]

PMID: 28938550

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Project description:Bladder cancer (BCa) is the tenth most common tumor in humans. DNA damage repair genes (DDRGs) play important roles in many malignant tumors; thus, their functions in BCa should also be explored. We performed a comprehensive analysis of the expression profiles of DDRGs in 410 BCa tumors and 19 normal tissues from The Cancer Genome Atlas database. We identified 123 DDRGs differentially expressed between BCa tumors and normal tissues, including 95 upregulated and 28 downregulated genes. We detected 22 DDRGs associated with overall survival (OS) of patients with BCa by performing univariate Cox regression analysis. To explore the interactions between OS-associated DDRGs, we constructed a PPI network, which showed that the top six DDRGs (CDCA2, FOXM1, PBK, RRM2, ORC1, and HDAC4) with the highest scores in the PPI network might play significant roles in OS of BCa. Moreover, to investigate the latent regulatory mechanism of these OS-associated DDRGs, we analyzed the transcription factors (TFs)-DDRGs regulatory network. The core seven TFs (NCAPG, DNMT1, LMNB1, BRCA1, E2H2, CENPA, and E2F7) were shown to be critical regulators of the OS-related DDRGs. The 22 DDRGs were incorporated into a stepwise multivariable Cox analysis. Then, we built the index of risk score based on the expression of 8 DDRGs (CAD, HDAC10, JDP2, LDLR, PDGFRA, POLA2, SREBF1, and STAT1). The p-value < 0.0001 in the Kaplan-Meier survival plot and an area under the ROC curve (AUC) of 0.771 in TCGA-BLCA training dataset suggested the high specificity and sensitivity of the prognostic index. Furthermore, we validated the risk score in the internal TCGA-BLCA and an independent GSE32894 dataset, with AUC of 0.743 and 0.827, respectively. More importantly, the multivariate Cox regression and stratification analysis demonstrated that the predictor was independent of various clinical parameters, including age, tumor stage, grade, and number of positive tumor lymph nodes. In summary, a panel of 8 DNA damage repair genes associated with overall survival in bladder cancer may be a useful prognostic tool.

Dataset Information

Prognostic value of DNA repair genes based on stratification of glioblastomas.

Publications

Prognostic value of DNA repair genes based on stratification of glioblastomas.

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