Methylation-driven genes and their prognostic value in cervical squamous cell carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Abnormal gene methylation is a key driver in tumor progression.
• Cervical squamous cell carcinoma (CESC) development involves complex genetic alterations.
• Identifying methylation-driven genes is crucial for understanding CESC pathogenesis.

Purpose of the Study:

• To explore methylation-driven genes in cervical squamous cell carcinoma (CESC).
• To identify key prognostic genes and establish a predictive risk signature for CESC.
• To investigate the potential of these genes as therapeutic targets.

Main Methods:

• Utilized The Cancer Genome Atlas (TCGA) database for CESC RNA expression, methylation, and clinical data.
• Constructed protein-protein interaction (PPI) networks and performed Gene Ontology (GO) and KEGG pathway analyses.
• Employed univariable/multivariate Cox regression, Kaplan-Meier, ROC curves, GSEA, and nomogram analysis to identify and validate prognostic genes.

Main Results:

• Identified 144 differentially expressed methylation-driven genes in CESC.
• Developed a risk model based on three prognostic genes: ITGA5, HHEX, and S1PR4.
• Found that specific methylation patterns of ITGA5, HHEX, and S1PR4 correlate with CESC patient prognosis, with a nomogram validating the model's performance.

Conclusions:

• Methylation-driven genes ITGA5, HHEX, and S1PR4 are significantly associated with CESC development and prognosis.
• These genes represent potential biomarkers for predicting CESC outcomes.
• ITGA5, HHEX, and S1PR4 may serve as novel therapeutic targets for cervical cancer treatment.