Biological Omics Analysis of Tumor Mutation Burden Combined with Immune Infiltrates in Uterine Corpus Endometrial Carcinoma

Background: In various malignancies, whether tumor mutation burden (TMB) is associated with improved survival outcomes or enhanced immunotherapy remains controversial. We are committed to exploring the prognosis of TMB and its potential association with immune infiltration of uterine corpus endometrial cancer (UCEC). Methods: : We downloaded transcriptome data and somatic mutation data from the Cancer Genome Atlas (TCGA) database, and visualized the mutation profiles using the "maftools" package. TMB was calculated and the samples were divided into two groups by the median. Kaplan-Meier analysis and Wilcoxon test were used to compare the differences in survival and clinicopathological characteristics. Furthermore, we performed functional enrichment analysis to screen for significant contributing pathways. The "CIBERSORT" package was used to estimate the abundance of immune components. Differential analysis was performed using the "limma" package to compare gene expression profiles. Multivariate analysis was used to identify risk genes related to TMB. Based on these genes, a risk model was established, and the receiver operating characteristic (ROC) curve was drawn to assess the predictive accuracy. Finally, we evaluated the relationship between risk genes and immune infiltration using the Timer database. Results: : The mutation data included 542 UCEC patients. The waterfall plot summarized the specific mutation information. Higher TMB levels indicated improved overall survival (OS) (p =0.048) and were associated with advanced grades. Pathway analysis showed that the differential signals were enriched in multiple immune-related crosstalks. We screened 108 differentially expressed genes in two TMB groups and identified four risk-related genes. The model based on these four risk genes had good predictive value, the area under the curve (AUC) = 0.670, and patients with higher risk scores showed worse OS (p <0.001). Additionally, CD8 T cells memory-activated, CD4 T cells, and M1 macrophages in the high TMB group showed higher infiltrates, while regulatory T cells (Tregs) and M2 macrophages showed lower infiltrates. Conclusions: : Higher TMB was associated with better survival outcomes and increased the immune infiltration in the tumor microenvironment of UCEC.