Objective To investigate the effect of lactate-related genes on the prognosis of endometrial cancer, construct a prognostic assessment model and validate its relevance to the immune microenvironment and clinical application.

Methods Based on a public database (TCGA-UCEC), a prognostic risk model (LMRGS) was constructed by bioinformatics screening of lactate-related genes; the predictive efficacy of the model was assessed using ROC curves, and external validation was performed on the GSE2882 dataset; differences in the immune function and checkpoint molecular expression between model subgroups were analyzed using ssGSEA; and key gene expression.

Results Ten key genes (ACADM, CYP27A1, CARS2, TIMM50, KY, SLC16A7, HPDL, LARGE1, and CLPB) were screened, and a total of 6 high-risk genes (HPDL, ACADM, CARS2, TIMM50, KY, and SLC16A7) were identified (HR ＞ 1). The high-risk groups (HPDL, TIMM50, CARS2, etc.) were all highly expressed in the late stage (stage Ⅲ/Ⅳ) (P ＜ 0.01 to P ＜ 0.05), and the patients' overall and median survival were shorter than that of the low-risk group (P ＜ 0.01).The 1/3/5-year AUC of the TCGA cohort was 0.716, 0.749, and 0.742, respectively; the 1/3-year AUC of external validation (GSE2882) was 0.79 and 0.810. Highly expressed immune functions in the low-risk group were Type II IFN Reponse, T cell co-stimulation, CCR, HLA and Check -point (P ＜ 0.05). The highly expressed immune cells in the high-risk group were CCL28, Low MICB, VEGFA, EZH2, SMC3, TIMD4 and LAG3 (P ＜ 0.05 to P ＜ 0.01). Experimental verification: TIMM50 was highly expressed in cancer tissues, and KY and SLC16A7 were lowly expressed (P ＜ 0.01), which was consistent with the bioinformatics results.

Conclusions Lactate-related gene prognostic model can effectively assess the prognosis and immunotherapy response of endometrial cancer patients, and the high-risk group is associated with immunosuppressive microenvironment, which provides a potential target for individualized treatment.