Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities

Bateman, NW; Abulez, T; Soltis, AR; McPherson, A; Choi, S; Garsed, DW; Pandey, A; Tian, C; Hood, BL; Conrads, KA; Teng, PN; Oliver, J; Gist, G; Mitchell, D; Litzi, TJ; Tarney, CM; Crothers, BA; Mhawech-Fauceglia, P; Dalgard, CL; Wilkerson, MD; Pierobon, M; Petricoin, EF; Yan, C; Meerzaman, D; Bodelon, C; Wentzensen, N; Lee, JSH; The APOLLO Research Network; Huntsman, DG; Shah, S; Shriver, CD; Phippen, NT; Darcy, KM; Bowtell, DDL; Conrads, TP; Maxwell, GL

Author(s): Bateman, NW; Abulez, T; Soltis, AR; McPherson, A; Choi, S; Garsed, DW; Pandey, A; Tian, C; Hood, BL; Conrads, KA; Teng, PN; Oliver, J; Gist, G; Mitchell, D; Litzi, TJ; Tarney, CM; Crothers, BA; Mhawech-Fauceglia, P; Dalgard, CL; Wilkerson, MD; Pierobon, M; Petricoin, EF; Yan, C; Meerzaman, D; Bodelon, C; Wentzensen, N; Lee, JSH; The APOLLO Research Network; Huntsman, DG; Shah, S; Shriver, CD; Phippen, NT; Darcy, KM; Bowtell, DDL; Conrads, TP; Maxwell, GL;
Details: Publication Year 2024-03-13,Volume 8,Issue #1,Page 68
Journal Title: NPJ Precision Oncology
Publication Type: Research article
Abstract: 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.
Publisher: Springer Nature
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1038/s41698-024-00519-8
Open Access at Publisher's Site: https://doi.org/10.1038/s41698-024-00519-8
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-03-28 06:48:07

Last Modified: 2024-03-28 06:51:46