Research on the Diagnostic Value and Immune Microenvironment Regulatory Mechanism of FOLR3 Gene in Endometrial Cancer Based on Multi-omics Data Algorithms

Background and ObjectiveFOLR3 serves as an important member of the folate metabolic pathway and plays a crucial role in various malignant tumors. However, the expression pattern, diagnostic value, and regulatory mechanism of FOLR3 in endometrial cancer (EC) remain unclear. This study aimed to explore the expression characteristics, clinical significance, and related molecular regulatory networks of FOLR3 in EC through bioinformatics analysis. MethodsTCGA datasets served as training sets, while GSE17025 from GEO served as validation sets. FOLR3 differential expression was analyzed using Wilcoxon rank-sum test, diagnostic efficacy evaluated by ROC curves, and prognostic value assessed via Kaplan-Meier survival analysis. Candidate genes were identified through WGCNA, univariate Cox regression, and differential expression analysis. Key genes were screened using machine learning algorithms (RF, LASSO, SVM-RFE) and PPI network analysis. ceRNA regulatory networks were constructed, and immune infiltration was analyzed using CIBERSORT. ResultsFOLR3 was significantly overexpressed in EC (P < 0.01) with diagnostic AUC values > 0.6 in both datasets. High FOLR3 expression indicated poor prognosis (HR=2.5, P < 0.05). Among 5,539 differentially expressed genes, 3 key genes (AURKA, POLQ, CDKN2A) were identified via multi-algorithm screening. Enrichment analysis showed involvement in cell division, p53 signaling, and cellular senescence. The ceRNA network comprised 72 nodes and 169 relationships, with KCNQ1OT1 and XIST as key lncRNA regulators. FOLR3 positively correlated with memory B cells and M0 macrophages, negatively with naive B cells and resting mast cells, with significant immune score differences (P < 0.05). ConclusionFOLR3 was significantly upregulated in EC, serving as an effective diagnostic biomarker and independent prognostic predictor. FOLR3 participated in tumorigenesis via complex ceRNA networks and regulated the tumor immune microenvironment. This study provides novel molecular targets and theoretical foundation for precision diagnosis and therapy of EC.