Introduction The TCGA molecular subtype of endometrial cancer has played a crucial role in predicting prognosis and guiding treatment. Specifically, the copy-number high (CNH) subtype has been associated with poor prognosis and marked heterogeneity. The tumour immune subtype provides a new perspective, and its combination with the molecular subtype facilitates precise diagnosis and treatment for patients.

Methods We collected 60 cases of CNH endometrial carcinoma in the TCGA database. Based on the enrichment scores of immune-related gene signatures, we used unsupervised cluster analysis to identify heterogeneous immune subtypes, and described their immune characteristics and prognosis. We also identified the prognostic marker through differential gene analysis and lasso regression analysis. Finally, we observed the distribution of the marker in tissues using immunohistochemical staining, and validated its prognostic value in independent samples.

Results We defined two immune subtypes, immune-hot (IH) and immune-cold (IC), which differed in immune cell infiltration, cytokine and chemokine expression and prognosis. The IH subtype has significantly stronger immune activation than the IC subtype, showing a significant infiltration of immune effector cells and high expression of relevant chemokines, with a better prognosis. By analyzing differentially expressed genes, we identified GZMM as a prognostic biomarker, confirming its unique prognostic value in CNH endometrial cancer. Additionally, we observed the correlation between GZMM and prognosis in immunohistochemical staining.

Conclusion/Implications This study revealed heterogeneous immune subtypes in CNH endometrial cancer and identified the prognostic biomarker GZMM. The stratified classification strategy combined with molecular and immune subtypes provides a reference for future clinical practice.