Machine learning-based neddylation landscape indicates different prognosis and immune microenvironment in endometrial cancer.

Endometrial cancer (EC) is women's fourth most common malignant tumor. Neddylation plays a significant role in many diseases; however, the effect of neddylation and neddylation-related genes (NRGs) on EC is rarely reported. In this study, we first used MLN4924 to affect the activation of neddylation in different cell lines (Ishikawa and HEC-1-A) and determined the critical role of neddylation-related pathways for EC progression. Subsequently, we screened 17 prognostic NRGs based on expression files of the TCGA-UCEC cohort. Based on unsupervised consensus clustering analysis, patients with EC were classified into two neddylation patterns (C1 and C2). In terms of prognosis, substantial differences were observed between the two patterns. Compared with C2, C1 exhibited low levels of immune infiltration and promoted tumor progression. More importantly, based on the expression of 17 prognostic NRGs, we transformed nine machine-learning algorithms into 89 combinations. The random forest (RSF) was selected to construct the neddylation-related risk score according to the average C-index of different cohorts. Notably, our score had important clinical implications for EC. Patients with high scores have poor prognoses and a cold tumor state. In conclusion, neddylation-related patterns and scores can distinguish tumor microenvironment (TME) and prognosis and guide personalized treatment in patients with EC.