npj Precision Oncology (Mar 2024)
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 L. Dalgard,
- Matthew D. Wilkerson,
- Mariaelena Pierobon,
- Emanuel F. Petricoin,
- Chunhua Yan,
- Daoud Meerzaman,
- Clara Bodelon,
- Nicolas Wentzensen,
- Jerry S. H. Lee,
- The APOLLO Research Network,
- David G. Huntsman,
- Sohrab Shah,
- Craig D. Shriver,
- Neil T. Phippen,
- Kathleen M. Darcy,
- David D. L. Bowtell,
- Thomas P. Conrads,
- G. Larry Maxwell
Affiliations
- Nicholas W. Bateman
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- Tamara Abulez
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- Anthony R. Soltis
- The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences
- Andrew McPherson
- Department of Computational Oncology, Memorial Sloan Kettering Cancer Center
- Seongmin Choi
- Department of Computational Oncology, Memorial Sloan Kettering Cancer Center
- Dale W. Garsed
- Peter MacCallum Cancer Centre, Parkville
- Ahwan Pandey
- Peter MacCallum Cancer Centre, Parkville
- Chunqiao Tian
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- Brian L. Hood
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- Kelly A. Conrads
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- Pang-ning Teng
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- Julie Oliver
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- Glenn Gist
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- Dave Mitchell
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- Tracy J. Litzi
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- Christopher M. Tarney
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- Barbara A. Crothers
- The Joint Pathology Center, Defense Health Agency, National Capital Region Medical Directorate
- Paulette Mhawech-Fauceglia
- Department of Anatomic Pathology, Division of Gynecologic Pathology, University of Southern California
- Clifton L. Dalgard
- The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences
- Matthew D. Wilkerson
- The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences
- Mariaelena Pierobon
- Center for Applied Proteomics and Molecular Medicine, George Mason University
- Emanuel F. Petricoin
- Center for Applied Proteomics and Molecular Medicine, George Mason University
- Chunhua Yan
- Center for Biomedical Informatics and Information Technology, National Cancer Institute
- Daoud Meerzaman
- Center for Biomedical Informatics and Information Technology, National Cancer Institute
- Clara Bodelon
- Division of Cancer Epidemiology and Genetics National Cancer Institute
- Nicolas Wentzensen
- Division of Cancer Epidemiology and Genetics National Cancer Institute
- Jerry S. H. Lee
- Ellison Institute for Transformative Medicine, University of Southern California
- The APOLLO Research Network
- David G. Huntsman
- Department of Pathology and Laboratory Medicine, The University of British Columbia
- Sohrab Shah
- Department of Computational Oncology, Memorial Sloan Kettering Cancer Center
- Craig D. Shriver
- The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University and Walter Reed National Military Medical Center
- Neil T. Phippen
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- Kathleen M. Darcy
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- David D. L. Bowtell
- Peter MacCallum Cancer Centre, Parkville
- Thomas P. Conrads
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- G. Larry Maxwell
- Gynecologic Cancer Center of Excellence, Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences
- DOI
- https://doi.org/10.1038/s41698-024-00519-8
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 17
Abstract
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.
