AGPAT4 Promotes Cervical Cancer Progression by Activating the PI3K/AKT Signaling Pathway: A Multi-Omics and Functional Study

Objective To investigate the role of AGPAT4 in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and its underlying mechanisms. Methods AGPAT4 expression and prognosis were analyzed using TCGA and GTEx data. Mendelian randomization (MR) was used to assess causality. Epigenetic regulation, immune microenvironment, and functional pathways were evaluated through methylation analysis, immune deconvolution, and enrichment analysis. The biological functions of AGPAT4 were validated in vitro and in vivo. Results AGPAT4 was downregulated in CESC but showed high diagnostic accuracy (AUC = 0.893). MR supported a causal link with cervical cancer risk (OR = 1.247, p = 0.008). High AGPAT4 expression was associated with worse overall, progression-free, and disease-specific survival, and served as an independent prognostic factor. Promoter hypermethylation was negatively correlated with AGPAT4 expression. AGPAT4-high tumors exhibited an immunosuppressive microenvironment and were enriched in PI3K-AKT signaling, extracellular matrix remodeling, and immune suppression pathways. Functionally, AGPAT4 overexpression promoted proliferation, migration, colony formation, and tumor growth, and activated the PI3K/AKT pathway. Conclusion AGPAT4 drives cervical cancer progression through PI3K/AKT pathway activation and immune microenvironment modulation, representing a potential diagnostic biomarker and therapeutic target.