Development of a seven-gene tumor immune microenvironment prognostic signature for high-risk grade III endometrial cancer

• Main Authors: Mingjun Zheng, Yuexin Hu, Rui Gou, Siting Li, Xin Nie, Xiao Li, Bei Lin
• Format: Article
• Language: English
• Published: Elsevier 2021-09-01
• Series: Molecular Therapy: Oncolytics
• Subjects: high-risk grade endometrial cancer; tumor immune microenvironment; gene signature; The Cancer Genome Atlas; immunotherapy
• Online Access: http://www.sciencedirect.com/science/article/pii/S2372770521000978

Uterine corpus endometrial carcinoma locally infiltrates numerous immune cells and other tumor immune microenvironment components. These cells are involved in malignant tumor growth and proliferation and the process of resistance toward immunotherapies. Here, we aimed to develop a tumor immune microenvironment-related prognostic signature for high-risk grade III endometrial carcinoma based on The Cancer Genome Atlas. The signature was systematically correlated with immune infiltration characteristics of the tumor microenvironment. The seven-gene Riskscore signature was robust and performed well in training, testing, and Gene Expression Omnibus-independent cohorts. A nomogram comprising the gene signature accurately predicted patient prognosis, with our model performing better than other endometrial cancer-related signatures. Analysis of the IMvigor210 immunotherapy cohort revealed that subgroups with a low Riskscore had a better prognosis than subgroups with a high Riskscore. Subgroups with a low Riskscore exhibited immune cell infiltration and inflammatory profiles, whereas subgroups with a high Riskscore experienced progressive disease. The receiver operating characteristic curve indicated that risk score, neoantigen, and tumor mutation burden models together accurately predicted treatment response. Taken together, we developed a tumor microenvironment-based seven-gene prognostic stratification system to predict the prognosis of patients with high-risk endometrial cancer and guide more effective immunotherapy strategies.