Comprehensive Analysis of Prognosis and Immune Landscapes Based on Lipid-Metabolism- and Ferroptosis-Associated Signature in Uterine Corpus Endometrial Carcinoma

(1) Background: The effect of tumor immunotherapy is influenced by the immune microenvironment, and it is unclear how lipid metabolism and ferroptosis regulate the immune microenvironment of uterine corpus endometrial carcinoma (UCEC). (2) Methods: Genes associated with lipid metabolism and ferroptosis (LMRGs-FARs) were extracted from the MSigDB and FerrDb databases, respectively. Five hundred and forty-four UCEC samples were obtained from the TCGA database. The risk prognostic signature was constructed by consensus clustering, univariate cox, and LASSO analyses. The accuracy of the risk modes was assessed through receiver operating characteristic (ROC) curve, nomogram, calibration,, and C-index analyses. The relationship between the risk signature and immune microenvironment was detected by the ESTIMATE, EPIC, TIMER, xCELL, quan-TIseq, and TCIA databases. The function of a potential gene, PSAT1, was measured by in vitro experiments. (3) Results: A six-gene (CDKN1A, ESR1, PGR, CDKN2A, PSAT1, and RSAD2) risk signature based on MRGs-FARs was constructed and evaluated with high accuracy in UCEC. The signature was identified as an independent prognostic parameter and it divided the samples into high- and low-risk groups. The low-risk group was positively associated with good prognosis, high mutational status, upregulated immune infiltration status, high expression of CTLA4, GZMA and PDCD1, anti-PD-1 treatment sensitivity, and chemoresistance. (4) Conclusions: We constructed a risk prognostic model based on both lipid metabolism and ferroptosis and evaluated the relationship between the risk score and tumor immune microenvironment in UCEC. Our study has provided new ideas and potential targets for UCEC individualized diagnosis and immunotherapy.