Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities
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Published:2024-03-13
Issue:1
Volume:8
Page:
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ISSN:2397-768X
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Container-title:npj Precision Oncology
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language:en
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Short-container-title:npj Precis. Onc.
Author:
Bateman Nicholas W.ORCID, Abulez TamaraORCID, Soltis Anthony R., McPherson Andrew, Choi Seongmin, Garsed Dale W.ORCID, Pandey Ahwan, Tian Chunqiao, Hood Brian L., Conrads Kelly A., Teng Pang-ningORCID, Oliver Julie, Gist Glenn, Mitchell Dave, Litzi Tracy J., Tarney Christopher M., Crothers Barbara A., Mhawech-Fauceglia Paulette, Dalgard Clifton L.ORCID, Wilkerson Matthew D., Pierobon MariaelenaORCID, Petricoin Emanuel F., Yan Chunhua, Meerzaman Daoud, Bodelon ClaraORCID, Wentzensen Nicolas, Lee Jerry S. H.ORCID, , Makohon-Moore Sasha C., Barakat Waleed, Zhang Xijun, Hunt Allison, Ao Wei, Lytle-Gabbin Stacey L., Casablanca Yovanni, Hamilton Chad A., Newell Miranda, Wells Justin, Sukumar Gauthaman, Bacikova Dagmar, Freyman John, Cohn David E., Berchuck Andrew, Havrilesky Laura, Duska Linda, Odunsi Adekunle, Sood Anil, Brenton James, Sala Evis, Annunziata Christina, Dorigo Oliver, Nelson Brad, Cochrane Dawn R., Moore Kathleen, Baldelli Elisa, Chen Qing-rong, Hu Ying, Fereday Sian, Traficante Nadia, DeFazio Anna, Goode Ellen L., Huntsman David G., Shah SohrabORCID, Shriver Craig D.ORCID, Phippen Neil T., Darcy Kathleen M.ORCID, Bowtell David D. L., Conrads Thomas P.ORCID, Maxwell G. Larry
Abstract
AbstractWe 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.
Funder
United States Department of Defense | Uniformed Services University of the Health Sciences Department of Health | National Health and Medical Research Council
Publisher
Springer Science and Business Media LLC
Reference62 articles.
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