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Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities.
Bateman, Nicholas W; Abulez, Tamara; Soltis, Anthony R; McPherson, Andrew; Choi, Seongmin; Garsed, Dale W; Pandey, Ahwan; Tian, Chunqiao; Hood, Brian L; Conrads, Kelly A; Teng, Pang-Ning; Oliver, Julie; Gist, Glenn; Mitchell, Dave; Litzi, Tracy J; Tarney, Christopher M; Crothers, Barbara A; Mhawech-Fauceglia, Paulette; Dalgard, Clifton L; Wilkerson, Matthew D; Pierobon, Mariaelena; Petricoin, Emanuel F; Yan, Chunhua; Meerzaman, Daoud; Bodelon, Clara; Wentzensen, Nicolas; Lee, Jerry S H; Huntsman, David G; Shah, Sohrab; Shriver, Craig D; Phippen, Neil T; Darcy, Kathleen M; Bowtell, David D L; Conrads, Thomas P; Maxwell, G Larry.
Afiliação
  • Bateman NW; Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. batemann@whirc.org.
  • Abulez T; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA. batemann@whirc.org.
  • Soltis AR; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University and Walter Reed National Military Medical Center, Bethesda, MD, USA. batemann@whirc.org.
  • McPherson A; Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Choi S; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA.
  • Garsed DW; The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Pandey A; Department of Computational Oncology, Memorial Sloan Kettering Cancer Center, Manhattan, NY, USA.
  • Tian C; Department of Computational Oncology, Memorial Sloan Kettering Cancer Center, Manhattan, NY, USA.
  • Hood BL; Peter MacCallum Cancer Centre, Parkville, Melbourne, Victoria, Australia.
  • Conrads KA; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
  • Teng PN; Peter MacCallum Cancer Centre, Parkville, Melbourne, Victoria, Australia.
  • Oliver J; Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Gist G; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA.
  • Mitchell D; Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Litzi TJ; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA.
  • Tarney CM; Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Crothers BA; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA.
  • Mhawech-Fauceglia P; Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Dalgard CL; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA.
  • Wilkerson MD; Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Pierobon M; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA.
  • Petricoin EF; Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Yan C; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA.
  • Meerzaman D; Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Bodelon C; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA.
  • Wentzensen N; Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Lee JSH; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA.
  • Huntsman DG; The Joint Pathology Center, Defense Health Agency, National Capital Region Medical Directorate, Silver Spring, MD, USA.
  • Shah S; Department of Anatomic Pathology, Division of Gynecologic Pathology, University of Southern California, Los Angeles, CA, USA.
  • Shriver CD; The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Phippen NT; The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Darcy KM; Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
  • Bowtell DDL; Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
  • Conrads TP; Center for Biomedical Informatics and Information Technology, National Cancer Institute, Rockville, MD, USA.
  • Maxwell GL; Center for Biomedical Informatics and Information Technology, National Cancer Institute, Rockville, MD, USA.
NPJ Precis Oncol ; 8(1): 68, 2024 Mar 13.
Article em En | MEDLINE | ID: mdl-38480868
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: NPJ Precis Oncol Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: NPJ Precis Oncol Ano de publicação: 2024 Tipo de documento: Article