Objective To investigate the prognostic impact of Piwi-interacting RNA (piRNA) pathway genes associated with phosphatase and tensin homolog (PTEN) in endometrial cancer.

Methods Based on The Cancer Genome Atlas (TCGA) database, 553 tumor samples of uterine corpus endometrial carcinoma (UCEC) and 35 normal samples were screened to obtain information on PTEN-associated piRNA pathway genes in endometrial cancer. A risk prognosis model was constructed and validated through differential gene screening, univariate Cox regression analysis, and LASSO Cox regression analysis. Protein-protein interaction (PPI) network and cytoHubba were employed to select Hub genes, followed by immune infiltration analysis.

Results A total of 167 differentially expressed genes were identified, and 18 genes associated with prognosis of patients were further determined. LASSO Cox regression analysis identified 11 genes (DUSP6, PTEN, MDM2, MAGI2, RAC3, AKT2, CDK6, KIT, IKBKB, BRAF, E2F2) that were closely related to the prognosis of endometrial cancer. The constructed risk prediction model yielded area under the curve (AUC) values of 0.780 and 0.733 in the training and validation sets, respectively. PPI network analysis revealed that PTEN, AKT2, MDM2, and KIT were key genes. Patients in the high-risk group exhibited a lower proportion of CD8 T cell infiltration and a transition of dendritic cells from a resting state to an activated state.

Conclusion The 11 identified genes may influence tumor development and immune response, and could serve as biomarkers for the prognosis of endometrial cancer.