Multimolecular characteristics of cell-death related hub genes in human cancers: a comprehensive pan-cancer analysis
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Published on: October 11, 2019
Dingtao Hu1,2, Tingyu Zhang3, Ziye Yan3
1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Anhui, China.
Abstract:
Failure of the normal process of cell death pathways contributes to the defection of immune systems and the occurrence of cancers. The key genes, the multimolecular mechanisms, and the immune functions of these genes in pan-cancers remain unclear. Using online databases of The Cancer Genome Atlas, GEPIA2, TISIDB, HPA, Kaplan-Meier Plotter, PrognoScan, cBioPortal, GSCALite, TIMER, and Sangerbox, we identified the key genes from the six primary cell death-related pathways and performed a comprehensive analysis to investigate the multimolecular characteristics and immunological functions of the hub genes in 33 human cancers. We identified five hub genes in the six primary cell death-related pathways (JUN, NFKB1, CASP3, PARP1, and TP53). We found that CASP3, PARP1, and TP53 were overexpressed in 28, 23, and 27 cancers. The expression of the five genes was associated with the development and prognosis of many cancers. Particularly, JUN, NFKB1, CASP3, and TP53 have prognostic values in Brain Lower Grade Glioma (LGG), while PARP1 and CASP3 could predict the survival outcomes in Adrenocortical carcinoma (ACC). In addition, an extensive association between five genes' expression, DNA methylation, and tumor-immune system interactions was noticed. The five cell death-related hub genes could function as potential biomarkers for various cancers, particularly LGG and ACC. The immunological function analysis of the five genes also proposes new targets for developing immunosuppressants and improving the immunotherapy efficacy of cancers. However, further extensive clinical and experimental research are required to validate their clinical values.
Insights
Dysfunctional cell death pathways drive cancer and immune defects. Five key genes (JUN, NFKB1, CASP3, PARP1, TP53) were identified as potential pan-cancer biomarkers and therapeutic targets, particularly for Lower Grade Glioma and Adrenocortical Carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Cell death pathway dysregulation is implicated in immune system defects and cancer development.
- Understanding the roles of key genes in these pathways across various cancers is crucial.
Purpose of the Study:
- To identify key genes in cell death pathways and analyze their molecular characteristics and immune functions in 33 human cancers.
- To investigate the potential of these genes as biomarkers and therapeutic targets.
Main Methods:
- Utilized multiple online databases including TCGA, GEPIA2, TISIDB, HPA, and TIMER.
- Performed comprehensive bioinformatic analysis of six primary cell death pathways.
- Investigated gene expression, prognosis association, DNA methylation, and tumor-immune interactions.
Main Results:
- Identified five hub genes: JUN, NFKB1, CASP3, PARP1, and TP53.
- CASP3, PARP1, and TP53 showed overexpression in numerous cancers.
- These genes demonstrated prognostic value in specific cancers like Lower Grade Glioma (LGG) and Adrenocortical Carcinoma (ACC).
- Found significant associations between gene expression, DNA methylation, and tumor-immune interactions.
Conclusions:
- The five identified cell death-related hub genes are potential biomarkers for various cancers, especially LGG and ACC.
- Their immunological functions suggest novel therapeutic targets for enhancing cancer immunotherapy and developing immunosuppressants.
- Further clinical validation is necessary to confirm their therapeutic potential.
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