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Updated: Oct 15, 2026
Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
Published on: October 25, 2011
Integrative Single-Cell and Bulk Transcriptomic Profiling Reveals Ferroptosis-Driven Heterogeneity of Ovarian Cancer
Haowen Zhang1, Zhiguang Zhang1, Xinxin Wu1
1Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People's Republic of China.
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.
Results:
OC epithelial cells were clustered into four subpopulations, which were further stratified into ferroptosis-high (EP_0 and EP_3) and ferroptosis-low (EP_1 and EP_2) groups. Key ferroptosis-associated epithelial patterns were reproduced in the independent GSE235329 scRNA-seq cohort. CellChat analysis identified MIF-(CD74+CXCR4) and MIF-(CD74+CD44) as prominent predicted interactions between OC epithelial cells and T cells. A validated three-gene prognostic model (OGN, RARRES1, IGFBP7) showed prognostic discrimination in the TCGA-OV cohort, with moderate predictive performance in the internal test set. Risk groups also differed in the xCell-estimated infiltration of selected immune and stromal cell populations.
Conclusion:
This study characterizes ferroptosis-associated heterogeneity of epithelial cells in OC at single-cell resolution and identifies candidate prognostic biomarkers and epithelial-immune communication signals that warrant further experimental and clinical validation.
