biostudies-literatureBateman NWNCI NIH HHSUnited States Department of Defense | Uniformed Services University of the Health SciencesDepartment of Health | National Health and Medical Research Council68https://www.ebi.ac.uk/biostudies/studies/S-EPMC10937683biostudies-literatureUnknown8(1)We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts. We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition.NPJ precision oncologyProteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities.PMC10937683HU0001-16-2-0006, HU0001-19-2-0031, HU0001-20-2-0033, and HU0001-21-2-0027HU0001-19-2-0031HU0001-16-2-00061092856, 1117044, 2008781, and 1186505P30 CA008748R01 CA248288P30 CA015083HU0001-21-2-00271092856, 1117044 and 2008781HU0001-20-2-0033HU0001-18-2-0032Soltis ARTraficante NHu YShah SHavrilesky LBarakat WWells JOdunsi AGarsed DWHunt AMhawech-Fauceglia PShriver CDPhippen NTAo WNelson BBateman NWPetricoin EFFreyman JDorigo OHamilton CATarney CMDalgard CLFereday SMaxwell GLBaldelli ESukumar GDuska LMakohon-Moore SCLee JSHBerchuck ASood APierobon MMeerzaman DDarcy KMCrothers BABowtell DDLBrenton JChoi SLitzi TJNewell MConrads TPAbulez TCohn DEHood BLCochrane DRPandey ALytle-Gabbin SLHuntsman DGAnnunziata CDeFazio ASala EWilkerson MDChen QRTian CMcPherson AGist GMoore KBacikova DCasablanca YWentzensen NAPOLLO Research NetworkBodelon CTeng PNZhang XOliver JYan CConrads KAMitchell DGoode ELfalseProteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities.We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts. We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition.2024-01-01T00:00:00Z2024 Mar2024-12-03T15:08:57.913Z2024-12-03T15:08:57.913ZS-EPMC109376833848086810.1038/s41698-024-00519-8