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 was validated through sample experiments.
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.
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