Discovery of a Ferroptosis-Related lncRNA–miRNA–mRNA Gene Signature in Endometrial Cancer Through a Comprehensive Co-Expression Network Analysis

<b>Background</b>: As a newly recognized type of cell death implicated in cancer, ferroptosis plays multiple roles in tumor biology. Here, we sought to construct a prognostic framework for EC on the basis of ferroptosis-related long non-coding RNAs (FerlncRNAs), microRNAs (FermiRNAs), and mRNAs (FRGs) for endometrial cancer (EC). <b>Methods</b>: Transcriptomic profiles of tumors and matched clinical data for 544 EC patients were retrieved from TCGA-UCEC. A prognostic framework was generated through Cox regression, integrating ferroptosis-linked lncRNAs, miRNAs, and mRNAs. EC cases were stratified into groups with high or low predicted risk based on ferroptosis-related gene expression. The model's prognostic utility was examined through Kaplan-Meier (K-M) analysis and receiver operating characteristic curves. <b>Results</b>: A prognostic model based on 16 RNAs, including 10 FerlncRNAs, 2 FermiRNAs, and 4 FRGs, was developed. Analysis using K-M plots showed that high-risk patients experienced shorter overall survival than their low-risk counterparts (<i>p</i> < 0.001). The model's area under curve (AUC) values were 0.731, 0.749, and 0.768 at 1-, 3-, and 5-year time points, surpassing those of standard clinical parameters. Furthermore, in an external validation cohort, these signature RNAs were associated with EC prognosis. <b>Conclusions</b>: The novel ferroptosis-related lncRNA-miRNA-mRNA prognostic model provides a basis to assess clinical prognosis in EC patients.