Multiomic analysis of CCNE1 amplification associated molecular and immune features in gynecological cancers

To delineate the genomic and cellular features of CCNE1 amplification across gynecologic cancer types using large-scale multi-omics data and assess its relevance for patient stratification and therapeutic targeting. We analyzed genomic and transcriptomic data from 12,845 patients with gynecological cancers curated from the cBioPortal database, including ovarian, endometrial, and cervical carcinomas. CCNE1 amplification rates, cooccurring genomic alterations, and pathway enrichment were evaluated. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomic data from cervical, endometrial, and ovarian tumors were used to investigate CCNE1 expression patterns, cell type specificity, and microenvironmental interactions. CCNE1 amplification was detected in 8.40% of all patients, with the highest rates in patients with ovarian cancer (8.01%) and endometrial cancer (5.06%). Among the ovarian subtypes, carcinosarcoma showed the highest amplification frequency (12.46%), followed by high-grade serous carcinoma (9.84%). Amplified tumors are frequently co-altered by TP53, PIK3CA, and PI3K-AKT pathway genes. Single-cell analyses revealed that CCNE1 expression was largely confined to epithelial cells and was associated with proliferative and structural remodeling pathways, with limited immune engagement across tumor types. Spatial transcriptomics confirmed the localization of CCNE1 in epithelial-rich regions and its correlation with adhesion- and motility-related genes in clear cell and high-grade serous ovarian carcinomas. CCNE1 amplification is enriched in aggressive histologic subtypes of gynecological cancers and is linked to epithelial-specific expression and immune exclusion. These findings indicate that CCNE1 represents a potential molecular marker for tumor aggressiveness, warranting further investigation in the context of patient stratification and therapeutic targeting.