Transcriptomic landscape of coexisting ovarian clear cell carcinoma and endometriosis: Insights into malignant transformation

Cancer Treat Res Commun. 2026:46:101098. doi: 10.1016/j.ctarc.2026.101098. Epub 2026 Jan 7.

Abstract

This study investigateted the malignant transformation of endometriosis (EMS) into ovarian clear cell carcinoma (OCCC) using spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) integration. Tissues with coexisting EMS and OCCC regions were analyzed to elucidate their molecular connections. Spatial transcriptomic profiling revealed shared molecular features between OCCC and EMS, including overexpression of genes related to tissue development and apoptosis. Integration with scRNA-seq data revealed that severe uterine EMS exhibited greater transcriptomic similarities to OCCC than to non-EAOC ovarian cancer subtypes, such as high-grade serous ovarian cancer (HGSOC). Further analysis classified the OCCC-specific genes into EMS epithelial cell-specific and tumor microenvironment (TME)-related categories, highlighting their roles in pathways associated with tumor progression, invasion, and metabolic reprogramming. These findings support the transcriptomic progression pathway from EMS to OCCC, and advance our understanding of the etiology of OCCC, suggesting strategies for targeted therapy and improved diagnostics.

Keywords: Endometriosis; Malignant transformation; Ovarian clear cell carcinoma; Single-cell RNA sequencing; spatial transcriptomics.

MeSH terms

  • Adenocarcinoma, Clear Cell* / genetics
  • Adenocarcinoma, Clear Cell* / pathology
  • Cell Transformation, Neoplastic* / genetics
  • Endometriosis* / complications
  • Endometriosis* / genetics
  • Endometriosis* / pathology
  • Female
  • Gene Expression Profiling
  • Humans
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Single-Cell Analysis
  • Transcriptome*
  • Tumor Microenvironment / genetics