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Identification of the prognostic immune subtype in copy-number high endometrial cancer
Mingyi Mao,Fang Jiang,Ruiqin Han,Yang Xiang 대한부인종양학회 2024 Journal of Gynecologic Oncology Vol.35 No.1
Objective: The TCGA molecular subtype of endometrial cancer (EC) is widely applied,among which the copy-number high (CNH) subtype has the poorest prognosis. However,the heterogeneity of this subtype remains elusive. In this study, we aimed to identif yheterogeneous immune subtypes in CNH EC and explore their prognostic significance. Methods: We collected 60 CNH EC cases in the TCGA database and performed unsuper visedcluster analysis based on the enrichment scores of immune-related gene signatures toidentif y immune subtypes. We described their immune characteristics and prognoses andconducted differential gene analysis and lasso regression to identif y a prognostic biomarker,GZMM. For experimental validation, we performed immunohistochemical staining of GZMMin 39 p53-positive EC surgical samples. Results: We defined two immune subtypes, immune-hot (IH) and immune-cold (IC), whichdiffered in immune cell infiltration, cytokine and chemokine expression and prognosis. TheIH subtype has significantly stronger immune activation than the IC subtype, showing asignificant infiltration of immune effector cells and high expression of relevant chemokines,with better prognosis. Moreover, the immunohistochemical staining of GZMM in a cohortof 39 p53-positive EC surgical samples confirmed GZMM as a unique prognostic biomarker,with high expression in both tumor cells and lymphocytes predicting a better prognosis. Conclusion: Our study revealed heterogeneous immune subtypes in CNH EC and identifiedGZMM as a prognostic biomarker. The stratified classification strategy combining molecularand immune subtypes provides valuable insights for future clinical practice.