Dataset Information

Set-Wise Differential Interaction Between Copy Number Alterations and Gene Expressions of Lower-Grade Glioma Reveals Prognosis-Associated Pathways.

ABSTRACT: The integrative analysis of copy number alteration (CNA) and gene expression (GE) is an essential part of cancer research considering the impact of CNAs on cancer progression and prognosis. In this research, an integrative analysis was performed with generalized differentially coexpressed gene sets (gdCoxS), which is a modification of dCoxS. In gdCoxS, set-wise interaction is measured using the correlation of sample-wise distances with Renyi's relative entropy, which requires an estimation of sample density based on omics profiles. To capture correlations between the variables, multivariate density estimation with covariance was applied. In the simulation study, the power of gdCoxS outperformed dCoxS that did not use the correlations in the density estimation explicitly. In the analysis of the lower-grade glioma of the cancer genome atlas program (TCGA-LGG) data, the gdCoxS identified 577 pathway CNAs and GEs pairs that showed significant changes of interaction between the survival and non-survival group, while other benchmark methods detected lower numbers of such pathways. The biological implications of the significant pathways were well consistent with previous reports of the TCGA-LGG. Taken together, the gdCoxS is a useful method for an integrative analysis of CNAs and GEs.

SUBMITTER: Cho SB

PROVIDER: S-EPMC7765960 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Set-Wise Differential Interaction Between Copy Number Alterations and Gene Expressions of Lower-Grade Glioma Reveals Prognosis-Associated Pathways.

Cho Seong Beom SB

Entropy (Basel, Switzerland) 20201218 12

The integrative analysis of copy number alteration (CNA) and gene expression (GE) is an essential part of cancer research considering the impact of CNAs on cancer progression and prognosis. In this research, an integrative analysis was performed with generalized differentially coexpressed gene sets (gdCoxS), which is a modification of dCoxS. In gdCoxS, set-wise interaction is measured using the correlation of sample-wise distances with Renyi's relative entropy, which requires an estimation of sa ...[more]

PMID: 33353229

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Project description:Cuproptosis a novel copper-dependent cell death modality, plays a crucial part in the oncogenesis, progression and prognosis of tumors. However, the relationships among DNA-methylation located in cuproptosis-related genes (CRGs), overall survival (OS) and the tumor microenvironment remain undefined. In this study, we systematically assessed the prognostic value of CRG-located DNA-methylation for lower-grade glioma (LGG). Clinical and molecular data were sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We employed Cox hazard regression to examine the associations between CRG-located DNA-methylation and OS, leading to the development of a prognostic signature. Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) analyses were utilized to gauge the accuracy of the signature. Gene Set Enrichment Analysis (GSEA) was applied to uncover potential biological functions of differentially expressed genes between high- and low-risk groups. A three CRG-located DNA-methylation prognostic signature was established based on TCGA database and validated in GEO dataset. The 1-year, 3-year, and 5-year area under the curve (AUC) of ROC curves in the TCGA dataset were 0.884, 0.888, and 0.859 while those in the GEO dataset were 0.943, 0.761 and 0.725, respectively. Cox-regression-analyses revealed the risk signature as an independent risk factor for LGG patients. Immunogenomic profiling suggested that the signature was associated with immune infiltration level and immune checkpoints. Functional enrichment analysis indicated differential enrichment in cell differentiation in the hindbrain, ECM receptor interactions, glycolysis and reactive oxygen species pathway across different groups. We developed and verified a novel CRG-located DNA-methylation signature to predict the prognosis in LGG patients. Our findings emphasize the potential clinical implications of CRG-located DNA-methylation indicating that it may serve as a promising therapeutic target for LGG patients.

Dataset Information

Set-Wise Differential Interaction Between Copy Number Alterations and Gene Expressions of Lower-Grade Glioma Reveals Prognosis-Associated Pathways.

Publications

Set-Wise Differential Interaction Between Copy Number Alterations and Gene Expressions of Lower-Grade Glioma Reveals Prognosis-Associated Pathways.

Similar Datasets

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