iScience (Jul 2021)
Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens
- Allison L. Hunt,
- Nicholas W. Bateman,
- Waleed Barakat,
- Sasha Makohon-Moore,
- Brian L. Hood,
- Kelly A. Conrads,
- Ming Zhou,
- Valerie Calvert,
- Mariaelena Pierobon,
- Jeremy Loffredo,
- Tracy J. Litzi,
- Julie Oliver,
- Dave Mitchell,
- Glenn Gist,
- Christine Rojas,
- Brian Blanton,
- Emma L. Robinson,
- Kunle Odunsi,
- Anil K. Sood,
- Yovanni Casablanca,
- Kathleen M. Darcy,
- Craig D. Shriver,
- Emanuel F. Petricoin,
- Uma N.M. Rao,
- G. Larry Maxwell,
- Thomas P. Conrads
Affiliations
- Allison L. Hunt
- Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Road, Annandale, VA 22042, USA; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Nicholas W. Bateman
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Waleed Barakat
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA
- Sasha Makohon-Moore
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA
- Brian L. Hood
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA
- Kelly A. Conrads
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA
- Ming Zhou
- Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Road, Annandale, VA 22042, USA; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Valerie Calvert
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA
- Mariaelena Pierobon
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA
- Jeremy Loffredo
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA
- Tracy J. Litzi
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA
- Julie Oliver
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA
- Dave Mitchell
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA
- Glenn Gist
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA
- Christine Rojas
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Brian Blanton
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Emma L. Robinson
- Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Road, Annandale, VA 22042, USA; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Kunle Odunsi
- Department of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
- Anil K. Sood
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA
- Yovanni Casablanca
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Kathleen M. Darcy
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Craig D. Shriver
- The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
- Emanuel F. Petricoin
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA
- Uma N.M. Rao
- Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., 6720A Rockledge Drive, Suite 100, Bethesda, MD 20817, USA
- G. Larry Maxwell
- Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Road, Annandale, VA 22042, USA; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Corresponding author
- Thomas P. Conrads
- Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Road, Annandale, VA 22042, USA; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; The John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA; Corresponding author
- Journal volume & issue
-
Vol. 24,
no. 7
p. 102757
Abstract
Summary: Enriched tumor epithelium, tumor-associated stroma, and whole tissue were collected by laser microdissection from thin sections across spatially separated levels of ten high-grade serous ovarian carcinomas (HGSOCs) and analyzed by mass spectrometry, reverse phase protein arrays, and RNA sequencing. Unsupervised analyses of protein abundance data revealed independent clustering of an enriched stroma and enriched tumor epithelium, with whole tumor tissue clustering driven by overall tumor “purity.” Comparing these data to previously defined prognostic HGSOC molecular subtypes revealed protein and transcript expression from tumor epithelium correlated with the differentiated subtype, whereas stromal proteins (and transcripts) correlated with the mesenchymal subtype. Protein and transcript abundance in the tumor epithelium and stroma exhibited decreased correlation in samples collected just hundreds of microns apart. These data reveal substantial tumor microenvironment protein heterogeneity that directly bears on prognostic signatures, biomarker discovery, and cancer pathophysiology and underscore the need to enrich cellular subpopulations for expression profiling.
