Introduction Although extensive research has been conducted on endometrial cancer and its hypoxic microenvironment, the role of DDIT4 in endometrial cancer remains unexplored. This study aimed to investigate the significance of DDIT4 as a prognostic biomarker for endometrial cancer using immunohistochemical staining and RNA-sequencing.

Methods Four types of endometrial cancer cells were cultured under normoxia and hypoxia conditions, and RNA-seq was used to examine differentially expressed genes. Immunohistochemical staining for DDIT4 and HIF1A was performed in 86 patients with type II endometrial cancer treated at our hospital. Statistical methods were used to analyze the correlation between DDIT4 expression and other clinicopathological factors and to assess its prognostic role.

Results The expression analysis of hypoxia-inducible genes using the four types of endometrial cancer cells revealed that DDIT4 was among the 28 genes upregulated in all cells. Our immunohistochemical analysis of DDIT4 expression in endometrial cancer tissues showed that high DDIT4 expression was significantly correlated with a favorable prognosis in both progression-free survival and overall survival according to univariate and multivariate COX regression analyses. In recurrent cases, metastasis only to lymph nodes was significantly related to high DDIT4 expression, whereas metastasis to other parenchymal organs was significantly dominant in patients with low DDIT4 expression.

Conclusion/Implications DDIT4 expression can predict survival and recurrence in type II endometrial cancer, indicating its potential use as a prognostic biomarker.