Epithelial characteristics of ovarian clear cell carcinoma at single-cell resolution

Ovarian clear cell carcinoma (OCCC) represents a rare and aggressive subtype of epithelial ovarian cancer with distinctive clinical and molecular characteristics. However, the identification, origin, and molecular features of the malignant epithelial cells in OCCC remain poorly studied. We establish an OCCC-associated transcriptional landscape using single-cell RNA sequencing and investigated the properties of epithelial cells in tissues from normal ovaries, ovarian endometriosis, primary OCCC and recurrent OCCC to assess the status of malignant epithelial cells. We identify a specific subcluster of malignant epithelial cells and further analyze them to discover 173 candidate factors associated with OCCC. Regulon and pseudotime trajectory analyses reveal six transcription factors (TFs) and their corresponding targets among these candidate factors, highlighting their roles in OCCC onset and reoccurrence. Through experimental validation, we confirm the crucial involvement of STAT3, KLF5, and TRIM28 in the proliferation and migration of OVISE cells. Silencing these three TFs also results in the down-regulation of their associated TF targets linked to OCCC. Overall, we characterize complex malignant-like cell populations at single-cell resolution and highlighted several TFs and their targets, providing essential resources for understanding the regulatory mechanisms underlying OCCC initiation and recurrence.