biostudies-literatureUnknownMetousis ANCI NIH HHSHigh-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 prmedRxiv : the preprint server for health sciences2025.08.25.25333715https://www.ebi.ac.uk/biostudies/studies/S-EPMC12407665biostudies-literatureIntegration of cell-type resolved spatial proteomics and transcriptomics reveals novel mechanisms in early ovarian cancer.PMC12407665R35 CA264619Richter SMetousis ALengyel EBen-Moshe SZhang JSamantaray TTheis FJKelliher LWang JMann MKrishnan RYamada SDRosenberger FANordmann TMKenny HALi YRavi MShimizu ASteigerwald SAlcazar IBilecz ALastra RSchweizer LfalseIntegration of cell-type resolved spatial proteomics and transcriptomics reveals novel mechanisms in early ovarian cancer.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 pr2025-01-01T00:00:00Z2025 Aug2026-04-25T03:16:33.25Z2026-04-25T03:15:14.035ZS-EPMC124076654090984110.1101/2025.08.25.25333715