Plate IV.82 · Publications
Integration of cell-type resolved spatial proteomics and transcriptomics reveals novel mechanisms in early ovarian cancer
Preprint in medRxiv, 28 August 2025.
Abstract
High-grade serous carcinoma (HGSC) is the most common ovarian cancer subtype, typically diagnosed at late stages with poor prognosis. Understanding early molecular events driving HGSC progression is crucial for timely detection and development of effective treatment strategies. We performed and integrated spatial cell-type resolved proteomics and paired transcriptomics across 25 women with precursor lesions of the fallopian tube and/or HGSC. Epithelial cell signatures revealed early activation of SUMOylation machinery, increased ATR and Wnt signaling, and enhanced MHC-I antigen presentation along the disease trajectory. The stroma exhibited extracellular matrix remodeling and interferon-mediated inflammation. Serous tubal intraepithelial carcinomas (STICs) in cancer patients contained a pro-coagulative signature and reduced APOA1/2 compared to STICs in individuals without cancer. We functionally established important roles of epithelial-derived TRIP13 and SUMOylation, and cancer-associated fibroblast-derived SULF1 and BGN in HGSC progression. These findings provide unique molecular insights into HGSC pathogenesis and identify potential new therapeutic targets for intervention.
Cite
@misc{metousis2025integration,
title = {{Integration of cell-type resolved spatial proteomics and transcriptomics reveals novel mechanisms in early ovarian cancer}},
author = {Metousis, Andreas and Kenny, Hilary A. and Shimizu, Aasa and Schweizer, Lisa and Ben-Moshe, Shani and Bilecz, Agnes and Krishnan, Rahul and Zhang, Jingwen and Alcazar, Isabel and Kelliher, Lucy and Ravi, Mallika and Samantaray, Tejas and Richter, Sabrina and Li, Yan and Wang, Jiying and Steigerwald, Sophia and Theis, Fabian J. and Rosenberger, Florian A. and Nordmann, Thierry M. and Yamada, S. Diane and Lastra, Ricardo and Mann, Matthias and Lengyel, Ernst},
howpublished = {medRxiv},
publisher = {openRxiv},
year = {2025},
month = aug,
doi = {10.1101/2025.08.25.25333715},
url = {https://doi.org/10.1101/2025.08.25.25333715},
note = {Preprint}
}