Integrative Single-Cell and Bulk Transcriptomic Profiling Reveals Ferroptosis-Driven Heterogeneity of Ovarian Cancer Epithelial Cells

Purpose

Ovarian cancer (OC) is a highly lethal gynecological malignancy characterized by insidious onset and poor prognosis, with limited validated prognostic biomarkers and therapeutic targets. Ferroptosis has been implicated in OC progression. However, most existing ferroptosis-related OC studies are based on bulk transcriptomic data, which fail to resolve the heterogeneity of OC epithelial cells. The relationship between ferroptosis-associated heterogeneity of epithelial cells and the tumor immune microenvironment remains insufficiently characterized at single-cell resolution. Materials and Methods: We integrated the GSE184880 single-cell RNA sequencing (scRNA-seq) discovery cohort, the independent GSE235329 scRNA-seq validation cohort, and bulk transcriptomic data from The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) cohort to analyze epithelial cell subpopulations, ferroptosis activity, differentiation trajectories, and intercellular communication, and to construct a prognostic model.