Identification of Differentially Methylated Genes as Potential Biomarkers for Early Diagnosis and Prognosis of Endometrial Cancer

Abstract

Objective: To identify methylated gene loci associated with uterine corpus endometrial carcinoma (UCEC) and evaluate their diagnostic and prognostic potential.

Methods: mRNA expression and DNA methylation data for UCEC were obtained from TCGA. Differential expression and methylation analyses were performed on eight candidate genes. Hypermethylated CG loci were screened based on logFC > 0.4 and assessed for diagnostic performance (sensitivity, specificity, AUC). The correlation between methylation and patient survival was analyzed using Kaplan-Meier curves. Methylation status was validated in normal (293T) and UCEC cell lines (ISHIKAWA, KLE).

Results: Six genes (AJAP1, GALR1, ZNF486, ZSCAN12, ZSCAN23, and CDO1) were significantly downregulated and hypermethylated in UCEC tumors. Key hypermethylated CG loci demonstrated high specificity (>95%) and AUC values (>80%) for distinguishing tumors and were significantly associated with patient survival. Experimental validation confirmed significantly elevated methylation levels for AJAP1, CDO1, GALR1, and ZSCAN12 in UCEC cell lines.

Conclusion: The identified methylation sites in AJAP1, GALR1, ZNF486, ZSCAN12, ZSCAN23, and CDO1 are closely associated with UCEC pathogenesis and prognosis, showing promise as diagnostic and prognostic biomarkers.