ObjectivesThe study aimed to investigate the genes linked with the progression of Endometrial cancer (EC) and discover promising new biomarkers for early detection. MethodsBased on the analysis of differentially expressed genes (DEGs), Series test of cluster (STC) and protein–protein interaction, potential hub genes involved in EC development were identified. The expression pattern, prognostic value, and diagnostic potential of ECT2 were investigated using clinical samples. ResultsThe DEGs showing an upward trend were significantly enriched in cancer-related processes and pathways. Through validations conducted across additional databases, eight potential hub genes for EC were identified: ASPM, ATAD2, BUB1B, ECT2, KIF14, NUF2, NCAPG, and SPAG5. Particularly, ECT2 exhibited the highest diagnostic efficacy. The expression levels of ECT2 varied significantly across different clinical stages, pathological grades, and metastasis statuses in UCEC. ECT2 mRNA was upregulated in the p53abn group, indicating a poorer prognosis, while it was lower in the MMRd and NSMP groups, indicating a moderate prognosis. In clinical samples, ECT2 showed an increasing trend from normal endometria and endometrial hyperplasia without atypia (EH) to atypical endometrial hyperplasia (AH) and EC. ECT2 effectively distinguished between Normal/EH and AH/EC. Patients with high expression of ECT2 had a more unfavourable prognosis. ConclusionsThe expression of ECT2 is significantly increased in cases of AH and EC. It has shown impressive accuracy in distinguishing between non-malignant and malignant endometria. These findings suggest that ECT2 has the potential to serve as a valuable biomarker for diagnosing endometrial neoplasia and as a prognostic indicator in EC.