Assessing the significance of CCNE1 overexpression in triple negative breast cancer.

PURPOSE: Cyclin E1 (CCNE1), a critical regulator of cell cycle progression, has been implicated in various cancers; however, its prognostic significance and functional role across breast cancer (BC) subtypes remain inadequately defined. This study aims to comprehensively analyze CCNE1 mRNA expression and evaluate its potential as both a prognostic biomarker and a therapeutic guide.

METHODS

We analyzed CCNE1 mRNA expression using large-scale BC cohorts (TCGA, METABRIC, GEO) and assessed associations with tumour grade, overall survival, and mutation status. The muTarget platform was employed to investigate associations between CCNE1 expression and key genetic alterations. Furthermore, gene set enrichment analysis was performed to identify enriched biological pathways, and functional studies were conducted using mTORC1 inhibition in TP53-mutant, RB1-deficient TNBC cells to evaluate cell viability and CCNE1 expression levels.

RESULTS

CCNE1 expression was significantly associated with higher tumour grade, overall survival, and distinct mutation statuses. Gene set enrichment analysis revealed enrichment of proliferation-related pathways, including G2-M checkpoint, E2F targets, and mTORC1 signaling in CCNE1-high tumors. Moreover, functional studies showed that mTORC1 inhibition successfully reduced CCNE1 expression and impaired viability in TP53-mutant, RB1-deficient TNBC cells.

CONCLUSIONS

CCNE1 overexpression characterises a clinically aggressive subset of breast cancers, particularly TNBC. Targeting mTORC1 may represent a promising therapeutic approach in CCNE1-high, TP53-mutated, and RB1-deficient tumours, supporting the clinical utility of CCNE1 in patient stratification and targeted therapy.