Correlation between the decreased expression of NUDT18 and tumor progression in endometrial cancer.

BACKGROUND: Nudix hydrolase 18 (NUDT18) belongs to the family of nudix hydrolases. This study aimed to clarify the relationship between NUDT18 and endometrial cancer (EC) and whether it is a prognostic factor for EC. METHODS: We first examined the function of NUDT18 through The Cancer Genome Atlas public data and Human Protein Atlas databases, and then immunohistochemical staining was conducted to compare the expression of NUDT18 in normal endometrium and EC tissues of different stages. Finally, we performed gene set enrichment analysis (GSEA) to identify the signaling pathways regulated by NUDT18 in EC. RESULTS: We found that NUDT18 expression was considerably elevated in EC tissues relative to physiological endometrium (P<0.001). However, Kaplan-Meier analysis revealed that high NUDT18 expression in EC was associated with a longer overall survival (OS). Immunohistochemistry results showed that NUDT18 expression was upregulated in tissues of early-stage EC compared with normal endometrial tissues and gradually decreased with the increase of stage. NUDT18 expression was significantly associated with Federation of Gynecology and Obstetrics stage, histologic grade, and myometrial invasion (all P values <0.05). GSEA revealed that the biological pathways that were differentially downregulated in the NUDT18-high expression phenotype were cell cycle, the TGF-β signaling pathway, RNA degradation, adherens junction, basal transcription factors, and DNA replication. In addition, NUDT18 DNA copy gain and the downregulation of miR-758-3p exhibited a correlation with the upregulation of NUDT18 in EC, and NUDT18 expression was significantly reduced in tumors with the TP53 mutation. The analysis of immune cell abundance indicated a substantial increase in immune infiltration in EC tissues with high NUDT18 expression. CONCLUSIONS: NUDT18 was upregulated in EC relative to normal endometrium, and its expression inversely correlated with tumor stage. Notably, higher NUDT18 expression predicted improved OS, highlighting its clinical significance as a marker of favorable prognosis in EC.