Jun Zhang1, Lanfen An1, Xing Zhou1, Rui Shi1, Hongbo Wang1. 1. Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract
BACKGROUND: Tumor mutational burden (TMB) is widely regarded as a predictor of response to immunotherapy. Few researchers have focused on the activity and prognosis of TMB in endometrial cancer (EC) and immune cells. Our study aimed to identify the prognostic role of TMB in EC. METHODS: We downloaded transcriptome data from The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analysis with log-rank test was conducted to assess the difference in overall survival (OS) between the high and low TMB groups. The "CIBERSORT" scripts were performed to evaluate the immune compositions of EC patients. Cox regression analysis and survival analysis were used to verify the prognostic value prognosis of TMB. RESULTS: We obtained the single nucleotide mutation data for 529 EC patients. A missense mutation was the most common mutation type. TMB was associated with survival outcome, tumor grades, and pathological types. We identified 10 hub TMB-related signature and found that elevated T-cell subsets infiltrating density in the high TMB group revealed improved survival outcomes. According to Kaplan-Meier analysis, T cells gamma delta and T cells regulatory were prognostic immune cells in EC samples. Moreover, many top gene set enrichment analysis (GSEA) results, including amino sugar and nucleotide sugar metabolism, nucleotide excision repair, or p53 signaling pathway, were enriched significantly with TMB level as phenotype. CONCLUSIONS: TMB is an important prognostic factor for EC, and TMB-related genes may be potential therapeutic targets for EC. 2021 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Tumor mutational burden (TMB) is widely regarded as a predictor of response to immunotherapy. Few researchers have focused on the activity and prognosis of TMB in endometrial cancer (EC) and immune cells. Our study aimed to identify the prognostic role of TMB in EC. METHODS: We downloaded transcriptome data from The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analysis with log-rank test was conducted to assess the difference in overall survival (OS) between the high and low TMB groups. The "CIBERSORT" scripts were performed to evaluate the immune compositions of EC patients. Cox regression analysis and survival analysis were used to verify the prognostic value prognosis of TMB. RESULTS: We obtained the single nucleotide mutation data for 529 EC patients. A missense mutation was the most common mutation type. TMB was associated with survival outcome, tumor grades, and pathological types. We identified 10 hub TMB-related signature and found that elevated T-cell subsets infiltrating density in the high TMB group revealed improved survival outcomes. According to Kaplan-Meier analysis, T cells gamma delta and T cells regulatory were prognostic immune cells in EC samples. Moreover, many top gene set enrichment analysis (GSEA) results, including amino sugar and nucleotide sugar metabolism, nucleotide excision repair, or p53 signaling pathway, were enriched significantly with TMB level as phenotype. CONCLUSIONS: TMB is an important prognostic factor for EC, and TMB-related genes may be potential therapeutic targets for EC. 2021 Annals of Translational Medicine. All rights reserved.
Entities:
Keywords:
Endometrial cancer (EC); immune cells; tumor mutational burden (TMB)
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