Endometrial cancer (UCEC) ranks among the most frequently diagnosed malignancies, with high-risk Grade III cases showing poor prognoses and a 5-year survival rate below 20%. Neutrophil extracellular traps (NETs) and the tumor immune microenvironment (TIME) influence cancer progression, but their roles in high-risk Grade III UCEC remain unclear. Expression profiles of high-risk Grade III UCEC patients were obtained from the TCGA database. Patients were clustered into subtypes based on NETs-TIME-related genes. Feature genes were identified using the Random Survival Forest (RSF) model to develop a prognostic risk score. The immune landscape, mutational characteristics, and drug sensitivity of risk subgroups were analyzed. Western blot validated protein expression of key genes in clinical tissues. 72 NETs-TIME-related genes classified 318 TCGA-UCEC patients into U1 and U2 subtypes. U2 showed a stronger anti-tumor immune response and better prognosis compared to U1. A four-gene signature (CCL4, MAPK7, CCL2, CCL5) generated a risk score: low-risk tumors displayed elevated immune infiltration and drug sensitivity, while high-risk tumors exhibited chromosomal amplification. Western blot confirmed upregulation of CCL2/CCL4/CCL5 and downregulation of MAPK7 in carcinoma tissues. A nomogram integrating the score further validated prognostic accuracy. The four-gene risk score accurately predicts prognosis in high-risk Grade III UCEC, offering a promising prognostic biomarker with experimental validation at the protein level.
Zhou et al. (Wed,) studied this question.