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

Nicholas W. Bateman*, Tamara Abulez, Anthony R. Soltis, Andrew McPherson, Seongmin Choi, Dale W. Garsed, Ahwan Pandey, Chunqiao Tian, Brian L. Hood, Kelly A. Conrads, Pang Ning Teng, Julie Oliver, Glenn Gist, Dave Mitchell, Tracy J. Litzi, Christopher M. Tarney, Barbara A. Crothers, Paulette Mhawech-Fauceglia, Clifton Dalgard, Matthew D. WilkersonMariaelena Pierobon, Emanuel F. Petricoin, Chunhua Yan, Daoud Meerzaman, Clara Bodelon, Nicolas Wentzensen, Jerry S.H. Lee, David G. Huntsman, Sohrab Shah, Craig D. Shriver, Neil T. Phippen, Kathleen M. Darcy, David D.L. Bowtell, Thomas P. Conrads*, G. Larry Maxwell*, Sasha C. Makohon-Moore, Waleed Barakat, Xijun Zhang, Allison Hunt, Wei Ao, Stacey L. Lytle-Gabbin, Yovanni Casablanca, Chad A. Hamilton, Miranda Newell, Justin Wells, Gauthaman Sukumar, Dagmar Bacikova, John Freyman, David E. Cohn, Andrew Berchuck, Laura Havrilesky, Linda Duska, Adekunle Odunsi, Anil Sood, James Brenton, Evis Sala, Christina Annunziata, Oliver Dorigo, Brad Nelson, Dawn R. Cochrane, Kathleen Moore, Elisa Baldelli, Qing Rong Chen, Ying Hu, Sian Fereday, Nadia Traficante, Anna DeFazio, Ellen L. Goode

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number68
Journalnpj Precision Oncology
Volume8
Issue number1
DOIs
StatePublished - Dec 2024

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