BACKGROUND: Abnormal gene methylation is crucial for tumor progression. This study explored a cluster of methylation-driven genes involved in cervical squamous cell carcinoma (CESC). METHODS: The data on RNA expression, methylation and clinical outcomes of CESC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Protein-protein interaction (PPI) network was constructed. Gene Ontology (GO) and KEGG analyses were performed to identify the biological functions of methylation-driven genes, and univariable and multivariate Cox analyses to screen out the key prognostic genes. A risk signature was established and its predictive value was evaluated with Kaplan-Meier and ROC curves. The key genes were further investigated by Cox regression analyses, gene set enrichment analysis (GSEA), and methylation site analysis. Additionally, "rms" package was used for establishing nomogram and calibrate curve. RESULTS: We found 144 differentially expressed methylation-driven genes. A risk model was constructed with three key prognostic genes (ITGA5, HHEX and S1PR4). The risk score was an independent risk factor for CESC prognosis. Lowly-expressed and hypermethylated ITGA5, highly-expressed and hypomethylated HHEX and S1PR4 were associated with better CESC prognosis. The methylation sites and biological functions enriched in ITGA5, HHEX and S1PR4 were uncovered. Additionally, the nomogram also validated the performance of risk model. CONCLUSIONS: Methylation-driven ITGA5, HHEX and S1PR4 are associated with CESC development. The three genes might serve as potential targets in the treatment of CESC. 2020 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Abnormal gene methylation is crucial for tumor progression. This study explored a cluster of methylation-driven genes involved in cervical squamous cell carcinoma (CESC). METHODS: The data on RNA expression, methylation and clinical outcomes of CESC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Protein-protein interaction (PPI) network was constructed. Gene Ontology (GO) and KEGG analyses were performed to identify the biological functions of methylation-driven genes, and univariable and multivariate Cox analyses to screen out the key prognostic genes. A risk signature was established and its predictive value was evaluated with Kaplan-Meier and ROC curves. The key genes were further investigated by Cox regression analyses, gene set enrichment analysis (GSEA), and methylation site analysis. Additionally, "rms" package was used for establishing nomogram and calibrate curve. RESULTS: We found 144 differentially expressed methylation-driven genes. A risk model was constructed with three key prognostic genes (ITGA5, HHEX and S1PR4). The risk score was an independent risk factor for CESC prognosis. Lowly-expressed and hypermethylated ITGA5, highly-expressed and hypomethylated HHEX and S1PR4 were associated with better CESC prognosis. The methylation sites and biological functions enriched in ITGA5, HHEX and S1PR4 were uncovered. Additionally, the nomogram also validated the performance of risk model. CONCLUSIONS: Methylation-driven ITGA5, HHEX and S1PR4 are associated with CESC development. The three genes might serve as potential targets in the treatment of CESC. 2020 Annals of Translational Medicine. All rights reserved.
Authors: Matthew E Ritchie; Belinda Phipson; Di Wu; Yifang Hu; Charity W Law; Wei Shi; Gordon K Smyth Journal: Nucleic Acids Res Date: 2015-01-20 Impact factor: 16.971
Authors: Hang Yuan; Ewa Krawczyk; Jan Blancato; Christopher Albanese; Dan Zhou; Naidong Wang; Siddartha Paul; Faris Alkhilaiwi; Nancy Palechor-Ceron; Aleksandra Dakic; Shuang Fang; Sujata Choudhary; Tung-Wei Hou; Yun-Ling Zheng; Bassem R Haddad; Yukari Usuda; Dan Hartmann; David Symer; Maura Gillison; Seema Agarwal; Danny Wangsa; Thomas Ried; Xuefeng Liu; Richard Schlegel Journal: Sci Rep Date: 2017-04-05 Impact factor: 4.379