Expression of ACTR3 in cervical cancer and impact on immune cell infiltration and prognosis: A comprehensive analysis based on bulk RNA-Seq and single-cell RNA-Seq

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BACKGROUND: PI3K/Akt/mTOR pathway is crucial in some cancers, but its relation with tumor-infiltrating immune cells in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is unanalyzed. This study aimed to determine if ACTR3 overexpression affects CC survival and explore its impact on the tumor immune microenvironment. METHODS: Research investigated ACTR3 expression levels related to PI3K/Akt/mTOR pathway and its influence on tumor immunology and clinical outcomes. Methods included RNA-seq data analysis, immune cell infiltration evaluation, survival analysis, gene enrichment analysis, and single-cell RNA-seq data integration. ACTR3 expression in cervical cancer specimens was evaluated by immunohistochemistry. RESULTS: Least absolute shrinkage and selection operator (LASSO) Cox regression identified ten key genes including ACTR3 with prognostic value. High ACTR3 expression correlated with poor outcomes, suggesting it as a prognostic biomarker. The prognostic model was validated by time-dependent receiver operating characteristic (ROC) curves for 1-, 3-, and 5-year survival. A nomogram combining ACTR3 expression and clinical parameters estimated patient survival. Single-cell RNA sequencing showed ACTR3-expressing immune cells in CESC include dendritic cells (DCs), T cells, and tissue stem cells. CONCLUSION: This research elucidated a distinct signature linked to the PI3K/Akt/mTOR signaling pathway, particularly focusing on ACTR3, which plays a role in both the onset and advancement of CESC. Moreover, ACTR3 has the potential to act as a prognostic biomarker for patients diagnosed with CESC, thereby offering novel perspectives for the development of clinical therapeutic approaches.

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