CCNE1 amplification indicates highly-aggressive component and suppressed immune status among different carcinomas

CCNE1 amplification (CCA) is a critical molecular alteration in tumors and a potential targetable for emerging therapies, however, its pan-cancer clinicopathological features and tumor immune microenvironment (TIME) characteristics remain poorly defined. This study compared CCA and non-amplified tumors across lung (LUAD), gastric (GA), ovarian (OV), and uterine (UC) carcinomas using our institutional cohort (n = 433) and public datasets (TCGA/cBioPortal), integrating histopathology, multi-omics, and detection validation (NGS/FISH/IHC). CCA exhibited aggressive histologic differentiation across tumor types, including the primitive enterocyte phenotype in GA, high-grade serous carcinoma/carcinosarcoma in UC/OV, and frequent neuroendocrine transformation in recurrent LUAD. All CCA groups had worse prognoses than their non-amplified counterparts. Cellular experiments validated the phenotypic transformation and unregulated proliferation following CCNE1 overexpression. Single-cell spatial transcriptomics and IHC revealed an immunosuppressive TIME across tumor types. Moreover, dual-color FISH demonstrated optimal detection consistency. This multi-cancer, multi-omics analysis establishes CCNE1 amplification as a hallmark of aggressive, immunoevasive carcinomas. This study integrated CCNE1-amplified carcinoma (CCA) pathological differentiation features across multiple cancer types from a histopathological perspective, breaking through single-organ limitations. In multiple cancer types, CCNE1 amplification indicates enhanced aggressiveness. Single-cell spatial transcriptomics was employed to analyze the tumor immune microenvironment characteristics of CCA.