ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
A Proteogenomic View of Synchronous Endometrioid Endometrial and Ovarian Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Case Report: Ovarian endometrioid tumor occurring in a patient with early-stage, low-risk endometrial carcinoma successfully treated by fertility-sparing management.Frontiers in oncology · 2025Article
- TGF-β-driven T-cell exclusion in ovarian cancer: single-cell and spatial transcriptomic views of immune low-response states.Frontiers in immunology · 2025Review
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10 authors.
Funding
Abstract
purposeIncreasing genomics-based evidence suggests that synchronous endometrial and ovarian cancer (SEOC) represents clonally related primary and metastatic tumors. A systematic analysis of the global protein landscape of SEOCs, heretofore lacking, could reveal functional and disease-specific consequences of known genetic alterations, the directionality of metastasis, and accurate histologic markers to distinguish SEOCs from single-site tumors. EXPERIMENTAL
designWe performed a systematic proteogenomic analysis of 29 patients diagnosed with SEOC at three international gynecologic oncology treatment centers (Chicago, Vancouver, and Tübingen). For direct comparison with single-site tumors, we included 9 patients with single-site endometrioid ovarian and 26 patients with single-site endometrioid endometrial cancer (EEC). For all 64 patients, we performed sequencing of a 275-gene cancer panel combined with compartment-resolved mass spectrometry-based proteomics of consecutive tissue sections to compare global (6,000+ proteins), tumor, and stromal proteomes.
resultsDNA-based panel sequencing confirmed that most SEOCs are clonally related. Global proteome profiling uncovered pronounced differences between SEOCs and single tumors and underscored the importance of the stromal proteome in defining and identifying SEOCs. We identified molecularly unique SEOC stromal proteomes, which were globally more related to single endometrial cancers. We finally derived a proteomic predictor distinguishing SEOCs from single-site ovarian and uterine tumors.
conclusionsThe integrated proteogenomic data show that SEOCs are distinguishable from endometrioid endometrial or endometrioid ovarian cancer. Based on their proteogenomic similarity to EECs, we conclude that most SEOCs represent primary EECs that have metastasized to the ovary.
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