Integrated identification, functional characterization, and clinical significance of key genes during cervical cancer progression
Introduction: Cervical cancer evolves from normal cervical epithelium through a multifaceted pathway, first to high-grade squamous intraepithelial lesions (HSILs) and subsequently culminating in invasive cancer, yet the specific molecular mechanisms driving this progression remain poorly understood. Objective: To identify genes persistently dysregulated during cervical lesion progression and to evaluate their clinical relevance with respect to prognosis, immune infiltration, and therapeutic response. Methods: Two independent gene expression datasets (GSE7803 and GSE64217) were analyzed to screen persistently differentially expressed genes (DEGs) across normal cervix, HSIL, and cervical cancer. Public databases and clinical samples were used to validate the hub genes initially identified through functional enrichment and protein–protein interaction analyses. Associations with patient survival, immune infiltration, and drug sensitivity were further analyzed using integrated bioinformatics platforms. Results: Eighteen common persistent DEGs were identified, primarily enriched in cell cycle regulation and epithelial differentiation. Four hub genes (AURKA, ECT2, RFC4, and PCNA) showed progressive upregulation as cervical lesions progressed and were associated with clinicopathological features. Elevated RFC4 and PCNA levels were significantly associated with improved survival. Immune analysis revealed distinct correlation patterns for RFC4 and PCNA expression: positive with B cells and effector memory immune cells, and negative with regulatory T cells. Drug sensitivity analysis showed that elevated RFC4 and PCNA expression were associated with lower IC50 values, whereas AURKA and ECT2 were linked to potential drug resistance. Conclusion: AURKA, ECT2, RFC4, and PCNA are key regulators of cervical lesion progression, among which RFC4 and PCNA are promising prognostic biomarkers and potential therapeutic targets.