Integrated Spatial Analysis Reveals the Molecular Landscape of Ovarian Precancerous Lesions
Studying precancerous lesions is essential for improving early detection and prevention, particularly in aggressive cancers such as ovarian carcinoma. Here, we conducted integrated and spatial analyses of transcriptomes, aneuploidy, and clinicopathological features in 166 ovarian precancerous lesions. Four pre-cancerous transcriptomic subtypes were identified: proliferative, immunoreactive, dormant, and mixed. These subtypes varied in their frequency of germline-BRCA1/2 mutations, aneuploidy, CCNE1/MYC amplification, proliferative activity, immune-regulatory gene expression, and histological features. Notably, the immunoreactive subtype upregulated immune-regulatory genes, exhibited chronic inflammation, and was enriched in cases with germline-BRCA1/2 mutations, deletions of chromosomes 17 (harboring TP53 and BRCA1) and 13 (harboring BRCA2), leading to a double "two-hit" involving TP53 and BRCA1/2. Tumor invasion was associated with the activation of interferon response pathways, epithelial-mesenchymal transition, and extracellular matrix remodeling. In summary, these results elucidate the earliest molecular landscape of ovarian precancerous lesions, serving as the foundation for future risk stratification to identify aggressive pre-cancerous lesions.
Authors
- Brant G. Wang (ORCID: https://orcid.org/0000-0002-1329-1586)
- Tu-Yung Chang (ORCID: https://orcid.org/0009-0007-8589-7775)
- Tricia Numan (ORCID: https://orcid.org/0000-0003-2855-0867)
- M. Herman Chui (ORCID: https://orcid.org/0000-0002-7220-3996)
- Rebecca L. Stone (ORCID: https://orcid.org/0000-0003-3590-5152)
- Leslie Cope (ORCID: https://orcid.org/0000-0002-4098-3289)
- Christopher Douville (ORCID: https://orcid.org/0000-0002-2510-4151)
- Yen‐Wei Chien (ORCID: https://orcid.org/0009-0003-4202-6735)
- Nickolas Papadopoulos (ORCID: https://orcid.org/0000-0001-7135-7451)
- Yeh Wang (ORCID: https://orcid.org/0000-0003-3185-4802)
- Ie−Ming Shih (ORCID: https://orcid.org/0000-0002-1084-2071)
- Tian‐Li Wang (ORCID: https://orcid.org/0000-0002-7082-449X)
- Thomas R. Pisanic (ORCID: https://orcid.org/0000-0001-5796-0836)
- S. S. Chen (ORCID: https://orcid.org/0000-0003-0756-6317)
- Annelise Sokolow (ORCID: https://orcid.org/0009-0007-4461-3123)
Institutions
- Roswell Park Comprehensive Cancer Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Johns Hopkins University (US)
- Baylor College of Medicine (US)
- Johns Hopkins Medicine (US)
- Johns Hopkins Bayview Medical Center (US)
- Johns Hopkins University Applied Physics Laboratory (US)
- Johns Hopkins Hospital (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
- Taipei Medical University (TW)
Publication Details
- Journal
- Cancer Research
- Published
- 2025-12-18
- DOI
- https://doi.org/10.1158/0008-5472.can-25-3189
- Primary Topic
- Ovarian cancer diagnosis and treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00